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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Ticagrelor monotherapy beats DAPT in STEMI
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
AT TCT 2020
New technologies show promise for treating pigmented lesions
carry a higher risk for postinflammatory hyperpigmentation than intense pulsed light or the long-pulsed laser, according to Mathew M. Avram, MD, JD.
For treating melanosomes with selective photothermolysis, some of the peak wavelengths include 532 nm, 694 nm, 755 nm, and 1064 nm, Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said during the virtual annual Masters of Aesthetics Symposium. “The ideal target is fair skin with a dark, pigmented lesion,” he said. “That way you’re going to get energy focused to the melanin that’s in the lesion itself.”
Q-switched and picosecond lasers are effective for pigmented lesions. These employ as much energy as the city of Boston for 20-30 billionths of a second, or 750 picoseconds. “This raises the temperature to 1,000° C in that time, which produces the characteristic epidermal whitening,” he said. “This targets pigment cells only, whether it’s exogenous or endogenous pigment.”
Benign pigmented lesions amenable to the Q-switched nanosecond and picosecond laser include lentigines and nevus of Ota/Ito. The mechanism of action for clinical lightening is fragmentation and release of melanin-laden cells and the gradual uptake and removal of fragments by activated macrophages into lymphatic vessels. “For effective results, do not blindly memorize settings or replicate recommended settings from a colleague or a device manufacturer,” advised Dr. Avram, who practiced law prior to becoming a physician. “Some lasers are not externally calibrated, so what you have to do is pay attention to the laser endpoint, which in this case is epidermal whitening. Tissue ‘splatter’ is an unsafe endpoint and may lead to scarring. Safe and unsafe laser endpoints and close clinical observation are the best means to avoid complications and get the best results for your patients. The key finding is the endpoint, not the energy settings.”
Pigmented lesions that should not be treated with a laser include atypical nevi, lentigo maligna, and other forms of melanoma. “When in doubt, perform a biopsy,” he said. “Regardless of who referred the case, you are liable if you treat a melanoma with a laser. This is not only misdiagnosis but it probably delays diagnosis as well. If you cannot recognize basis pigmented lesion morphology, do not treat pigmented lesions. At some point, it’s going to catch up with you.”
Patients with more pigment to their skin face a higher risk for postinflammatory hyperpigmentation, Dr. Avram continued. While longer pulsed lasers produce less hyperpigmentation, they’re also less effective at getting rid of lesions. “You can combine a long-pulsed laser with fractional resurfacing or IPL [intense pulsed light] to optimize improvement,” he said. “If you don’t have two lasers to use, you can just use a longer-pulsed laser. The desired treatment endpoint for this approach is an ashen gray appearance.” Options include a 532-nm Nd:YAG laser with or without cooling, a 595-nm pulsed dye laser without cooling, and a 755-nm alexandrite laser without cooling.
One advance in the treatment of seborrheic keratoses is Nano-Pulse Stimulation (NPS), a novel technology being developed by Pulse Biosciences. With this approach, nanosecond electrical energy pulses cause internal organelle disruption, which leads to regulated cell death. “The cell-specific effect is nonthermal, as a typical nano-pulse delivers 0.1 joules of energy distributed in a volume of tissue,” Dr. Avram said. Early human studies established safe doses and validation of mechanism hypothesis for benign-lesion efficacy. “What you have are tiny nanopores that allow calcium ions to flow into the cell,” he explained. “The nanopores in the endoplasmic reticulum allow calcium ions to flow out of the endoplasmic reticulum, stressing it. These nanopores in the mitochondria disrupt the ability to generate energy, and the cell dies.”
Histology has revealed that within days the procedure causes regulated cell death with no thermal effects. The ability of NPS energy to clear seborrheic keratoses (SK) was confirmed in a study of 58 subjects who had 174 SK lesions treated. The majority of SKs (82%) were rated as clear or mostly clear 106 days post treatment. All results reflected a single treatment session.
Another novel treatment, “cryomodulation,” a technology being developed by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry Chan, MD, PhD, expresses cold-induced change to the skin as a way to pause melanin production. “You get melanin production paused but melanocyte function is preserved,” Dr. Avram explained. “There is a normal epidermal barrier and no persistent inflammatory response, so there’s no hyperpigmentation.” He characterized it as an ease-of-use clinical procedure for treating benign lesions in all skin types. A mask is applied to confine freezing to the desired treatment area, and hydrated gauze is used to help facilitate ice crystal propagation. A prototype of the device features a parameter selection based on lesion type, anatomical location, and skin type. “It uses between 107 and 166 kJ/m2 of extracted energy, and you take photos at baseline and follow-up,” he said. “You get 2-3 days of redness, darkening, and swelling. It’s well tolerated, with minimal discomfort. There’s no long-term dyschromia. This is nice, because patients have little, if any, downtime.”
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton. He also reported having ownership and/or shareholder interest in Cytrellis.
carry a higher risk for postinflammatory hyperpigmentation than intense pulsed light or the long-pulsed laser, according to Mathew M. Avram, MD, JD.
For treating melanosomes with selective photothermolysis, some of the peak wavelengths include 532 nm, 694 nm, 755 nm, and 1064 nm, Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said during the virtual annual Masters of Aesthetics Symposium. “The ideal target is fair skin with a dark, pigmented lesion,” he said. “That way you’re going to get energy focused to the melanin that’s in the lesion itself.”
Q-switched and picosecond lasers are effective for pigmented lesions. These employ as much energy as the city of Boston for 20-30 billionths of a second, or 750 picoseconds. “This raises the temperature to 1,000° C in that time, which produces the characteristic epidermal whitening,” he said. “This targets pigment cells only, whether it’s exogenous or endogenous pigment.”
Benign pigmented lesions amenable to the Q-switched nanosecond and picosecond laser include lentigines and nevus of Ota/Ito. The mechanism of action for clinical lightening is fragmentation and release of melanin-laden cells and the gradual uptake and removal of fragments by activated macrophages into lymphatic vessels. “For effective results, do not blindly memorize settings or replicate recommended settings from a colleague or a device manufacturer,” advised Dr. Avram, who practiced law prior to becoming a physician. “Some lasers are not externally calibrated, so what you have to do is pay attention to the laser endpoint, which in this case is epidermal whitening. Tissue ‘splatter’ is an unsafe endpoint and may lead to scarring. Safe and unsafe laser endpoints and close clinical observation are the best means to avoid complications and get the best results for your patients. The key finding is the endpoint, not the energy settings.”
Pigmented lesions that should not be treated with a laser include atypical nevi, lentigo maligna, and other forms of melanoma. “When in doubt, perform a biopsy,” he said. “Regardless of who referred the case, you are liable if you treat a melanoma with a laser. This is not only misdiagnosis but it probably delays diagnosis as well. If you cannot recognize basis pigmented lesion morphology, do not treat pigmented lesions. At some point, it’s going to catch up with you.”
Patients with more pigment to their skin face a higher risk for postinflammatory hyperpigmentation, Dr. Avram continued. While longer pulsed lasers produce less hyperpigmentation, they’re also less effective at getting rid of lesions. “You can combine a long-pulsed laser with fractional resurfacing or IPL [intense pulsed light] to optimize improvement,” he said. “If you don’t have two lasers to use, you can just use a longer-pulsed laser. The desired treatment endpoint for this approach is an ashen gray appearance.” Options include a 532-nm Nd:YAG laser with or without cooling, a 595-nm pulsed dye laser without cooling, and a 755-nm alexandrite laser without cooling.
One advance in the treatment of seborrheic keratoses is Nano-Pulse Stimulation (NPS), a novel technology being developed by Pulse Biosciences. With this approach, nanosecond electrical energy pulses cause internal organelle disruption, which leads to regulated cell death. “The cell-specific effect is nonthermal, as a typical nano-pulse delivers 0.1 joules of energy distributed in a volume of tissue,” Dr. Avram said. Early human studies established safe doses and validation of mechanism hypothesis for benign-lesion efficacy. “What you have are tiny nanopores that allow calcium ions to flow into the cell,” he explained. “The nanopores in the endoplasmic reticulum allow calcium ions to flow out of the endoplasmic reticulum, stressing it. These nanopores in the mitochondria disrupt the ability to generate energy, and the cell dies.”
Histology has revealed that within days the procedure causes regulated cell death with no thermal effects. The ability of NPS energy to clear seborrheic keratoses (SK) was confirmed in a study of 58 subjects who had 174 SK lesions treated. The majority of SKs (82%) were rated as clear or mostly clear 106 days post treatment. All results reflected a single treatment session.
Another novel treatment, “cryomodulation,” a technology being developed by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry Chan, MD, PhD, expresses cold-induced change to the skin as a way to pause melanin production. “You get melanin production paused but melanocyte function is preserved,” Dr. Avram explained. “There is a normal epidermal barrier and no persistent inflammatory response, so there’s no hyperpigmentation.” He characterized it as an ease-of-use clinical procedure for treating benign lesions in all skin types. A mask is applied to confine freezing to the desired treatment area, and hydrated gauze is used to help facilitate ice crystal propagation. A prototype of the device features a parameter selection based on lesion type, anatomical location, and skin type. “It uses between 107 and 166 kJ/m2 of extracted energy, and you take photos at baseline and follow-up,” he said. “You get 2-3 days of redness, darkening, and swelling. It’s well tolerated, with minimal discomfort. There’s no long-term dyschromia. This is nice, because patients have little, if any, downtime.”
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton. He also reported having ownership and/or shareholder interest in Cytrellis.
carry a higher risk for postinflammatory hyperpigmentation than intense pulsed light or the long-pulsed laser, according to Mathew M. Avram, MD, JD.
For treating melanosomes with selective photothermolysis, some of the peak wavelengths include 532 nm, 694 nm, 755 nm, and 1064 nm, Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said during the virtual annual Masters of Aesthetics Symposium. “The ideal target is fair skin with a dark, pigmented lesion,” he said. “That way you’re going to get energy focused to the melanin that’s in the lesion itself.”
Q-switched and picosecond lasers are effective for pigmented lesions. These employ as much energy as the city of Boston for 20-30 billionths of a second, or 750 picoseconds. “This raises the temperature to 1,000° C in that time, which produces the characteristic epidermal whitening,” he said. “This targets pigment cells only, whether it’s exogenous or endogenous pigment.”
Benign pigmented lesions amenable to the Q-switched nanosecond and picosecond laser include lentigines and nevus of Ota/Ito. The mechanism of action for clinical lightening is fragmentation and release of melanin-laden cells and the gradual uptake and removal of fragments by activated macrophages into lymphatic vessels. “For effective results, do not blindly memorize settings or replicate recommended settings from a colleague or a device manufacturer,” advised Dr. Avram, who practiced law prior to becoming a physician. “Some lasers are not externally calibrated, so what you have to do is pay attention to the laser endpoint, which in this case is epidermal whitening. Tissue ‘splatter’ is an unsafe endpoint and may lead to scarring. Safe and unsafe laser endpoints and close clinical observation are the best means to avoid complications and get the best results for your patients. The key finding is the endpoint, not the energy settings.”
Pigmented lesions that should not be treated with a laser include atypical nevi, lentigo maligna, and other forms of melanoma. “When in doubt, perform a biopsy,” he said. “Regardless of who referred the case, you are liable if you treat a melanoma with a laser. This is not only misdiagnosis but it probably delays diagnosis as well. If you cannot recognize basis pigmented lesion morphology, do not treat pigmented lesions. At some point, it’s going to catch up with you.”
Patients with more pigment to their skin face a higher risk for postinflammatory hyperpigmentation, Dr. Avram continued. While longer pulsed lasers produce less hyperpigmentation, they’re also less effective at getting rid of lesions. “You can combine a long-pulsed laser with fractional resurfacing or IPL [intense pulsed light] to optimize improvement,” he said. “If you don’t have two lasers to use, you can just use a longer-pulsed laser. The desired treatment endpoint for this approach is an ashen gray appearance.” Options include a 532-nm Nd:YAG laser with or without cooling, a 595-nm pulsed dye laser without cooling, and a 755-nm alexandrite laser without cooling.
One advance in the treatment of seborrheic keratoses is Nano-Pulse Stimulation (NPS), a novel technology being developed by Pulse Biosciences. With this approach, nanosecond electrical energy pulses cause internal organelle disruption, which leads to regulated cell death. “The cell-specific effect is nonthermal, as a typical nano-pulse delivers 0.1 joules of energy distributed in a volume of tissue,” Dr. Avram said. Early human studies established safe doses and validation of mechanism hypothesis for benign-lesion efficacy. “What you have are tiny nanopores that allow calcium ions to flow into the cell,” he explained. “The nanopores in the endoplasmic reticulum allow calcium ions to flow out of the endoplasmic reticulum, stressing it. These nanopores in the mitochondria disrupt the ability to generate energy, and the cell dies.”
Histology has revealed that within days the procedure causes regulated cell death with no thermal effects. The ability of NPS energy to clear seborrheic keratoses (SK) was confirmed in a study of 58 subjects who had 174 SK lesions treated. The majority of SKs (82%) were rated as clear or mostly clear 106 days post treatment. All results reflected a single treatment session.
Another novel treatment, “cryomodulation,” a technology being developed by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry Chan, MD, PhD, expresses cold-induced change to the skin as a way to pause melanin production. “You get melanin production paused but melanocyte function is preserved,” Dr. Avram explained. “There is a normal epidermal barrier and no persistent inflammatory response, so there’s no hyperpigmentation.” He characterized it as an ease-of-use clinical procedure for treating benign lesions in all skin types. A mask is applied to confine freezing to the desired treatment area, and hydrated gauze is used to help facilitate ice crystal propagation. A prototype of the device features a parameter selection based on lesion type, anatomical location, and skin type. “It uses between 107 and 166 kJ/m2 of extracted energy, and you take photos at baseline and follow-up,” he said. “You get 2-3 days of redness, darkening, and swelling. It’s well tolerated, with minimal discomfort. There’s no long-term dyschromia. This is nice, because patients have little, if any, downtime.”
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton. He also reported having ownership and/or shareholder interest in Cytrellis.
FROM MOA 2020
Being HIV positive increases risk of death from COVID-19
compared with people without HIV.
A comparison of outcomes of people with HIV to people without HIV who were hospitalized in the United Kingdom with COVID-19 from Jan. 17 to June 4 showed that HIV-positive status was associated with a 63% increased risk of day 28 mortality.
This was especially true for HIV+ patients younger than 70 years of age, said Anna Maria Geretti, MD, PhD, professor of virology and infectious diseases, University of Liverpool, England.
The results are from an analysis of data from the ISARIC World Health Organization (WHO) Clinical Characterisation Protocol (UK) study, and were presented at the HIV Glasgow annual meeting, held virtually this year because of the pandemic.
“We investigated whether HIV status could be important in COVID-19 outcomes because there was anxiety on the part of our patients, and we wanted to gather some evidence-based information in order to help guide them,” Dr. Geretti said in an interview.
“ISARIC is an international protocol and the UK is one of the nations participating. We applied for access to its very large database, which connects data from all patients who are hospitalized with either known or suspected COVID-19. We wanted to see specifically how the presentation and outcomes of patients with HIV compared with the rest of the population without HIV. It afforded us an ideal opportunity to start to answer this question, and this is our first analysis in what will be an ongoing process. Importantly, we showed that there is a need to really look more carefully at the population with HIV,” she said.
Out of a total of 47,539 patients in the database, 115 (0.24%) had confirmed HIV-positive status, and 103 of those 115, or 89.6%, had a record of being on antiretroviral therapy.
On admission, the patients with HIV were younger, with a median age of 55 compared with 74 for patients without HIV (P < .001). They also had a higher prevalence of obesity, moderate to severe liver disease, higher lymphocyte counts and C-reactive protein, as well as more systemic symptoms.
There were no differences in respiratory rate, need for oxygen, or prevalence of chest infiltrates.
The cumulative incidence of mortality at day 28 was 25.2% in HIV-positive patients compared with 32.1% in HIV-negative patients (P = .12).
But when the researchers looked more closely, they noticed that the mortality rate was actually higher in younger HIV+ patients compared with HIV-negative patients.
Stratified by age, 28-day mortality was significantly higher in HIV+ patients aged <50 years (P =.004); and those aged 50 to 59 years (P = .05).
“So below the age of 70, the risk of mortality was double in people with HIV. The people with HIV who died often had diabetes with complications and also more frequent obesity, but this was not the only explanation,” Dr. Geretti said. “There is something to do with the HIV status per se.”
Next steps will be to expand the data set and repeat the analysis with an additional 100 patients “at least” she said.
The researchers also hope to zero in on what about being HIV+ is increasing the mortality risk from COVID-19.
“Right now we need greater numbers and we hope that the research community will be stimulated to take a closer look at this information, and merge other data so that we can strengthen confidence in the data and tease out what factors are causing this increased risk for mortality,” Dr. Geretti said.
She also emphasized that all patients admitted to hospital with COVID-19 should be asked about their HIV status.
“It is important that the HIV status be recorded if we want to increase our ability to understand how HIV impacts survival,” she stressed. “In our experience we found that most of the hospital records were not doing that. Since HIV+ patients seem to be at increased risk, HIV status should be factored into the clinical management. Ask patients if they are HIV+, and if it is not known, then do a test. That would be good practice.”
Dr. Geretti reported no relevant financial relationships. The work was supported by grants from the National Institute of Health Research, the Medical Research Council, the Wellcome Trust, the Department for International Development, and the Bill and Melinda Gates Foundation.
A version of this article originally appeared on Medscape.com.
compared with people without HIV.
A comparison of outcomes of people with HIV to people without HIV who were hospitalized in the United Kingdom with COVID-19 from Jan. 17 to June 4 showed that HIV-positive status was associated with a 63% increased risk of day 28 mortality.
This was especially true for HIV+ patients younger than 70 years of age, said Anna Maria Geretti, MD, PhD, professor of virology and infectious diseases, University of Liverpool, England.
The results are from an analysis of data from the ISARIC World Health Organization (WHO) Clinical Characterisation Protocol (UK) study, and were presented at the HIV Glasgow annual meeting, held virtually this year because of the pandemic.
“We investigated whether HIV status could be important in COVID-19 outcomes because there was anxiety on the part of our patients, and we wanted to gather some evidence-based information in order to help guide them,” Dr. Geretti said in an interview.
“ISARIC is an international protocol and the UK is one of the nations participating. We applied for access to its very large database, which connects data from all patients who are hospitalized with either known or suspected COVID-19. We wanted to see specifically how the presentation and outcomes of patients with HIV compared with the rest of the population without HIV. It afforded us an ideal opportunity to start to answer this question, and this is our first analysis in what will be an ongoing process. Importantly, we showed that there is a need to really look more carefully at the population with HIV,” she said.
Out of a total of 47,539 patients in the database, 115 (0.24%) had confirmed HIV-positive status, and 103 of those 115, or 89.6%, had a record of being on antiretroviral therapy.
On admission, the patients with HIV were younger, with a median age of 55 compared with 74 for patients without HIV (P < .001). They also had a higher prevalence of obesity, moderate to severe liver disease, higher lymphocyte counts and C-reactive protein, as well as more systemic symptoms.
There were no differences in respiratory rate, need for oxygen, or prevalence of chest infiltrates.
The cumulative incidence of mortality at day 28 was 25.2% in HIV-positive patients compared with 32.1% in HIV-negative patients (P = .12).
But when the researchers looked more closely, they noticed that the mortality rate was actually higher in younger HIV+ patients compared with HIV-negative patients.
Stratified by age, 28-day mortality was significantly higher in HIV+ patients aged <50 years (P =.004); and those aged 50 to 59 years (P = .05).
“So below the age of 70, the risk of mortality was double in people with HIV. The people with HIV who died often had diabetes with complications and also more frequent obesity, but this was not the only explanation,” Dr. Geretti said. “There is something to do with the HIV status per se.”
Next steps will be to expand the data set and repeat the analysis with an additional 100 patients “at least” she said.
The researchers also hope to zero in on what about being HIV+ is increasing the mortality risk from COVID-19.
“Right now we need greater numbers and we hope that the research community will be stimulated to take a closer look at this information, and merge other data so that we can strengthen confidence in the data and tease out what factors are causing this increased risk for mortality,” Dr. Geretti said.
She also emphasized that all patients admitted to hospital with COVID-19 should be asked about their HIV status.
“It is important that the HIV status be recorded if we want to increase our ability to understand how HIV impacts survival,” she stressed. “In our experience we found that most of the hospital records were not doing that. Since HIV+ patients seem to be at increased risk, HIV status should be factored into the clinical management. Ask patients if they are HIV+, and if it is not known, then do a test. That would be good practice.”
Dr. Geretti reported no relevant financial relationships. The work was supported by grants from the National Institute of Health Research, the Medical Research Council, the Wellcome Trust, the Department for International Development, and the Bill and Melinda Gates Foundation.
A version of this article originally appeared on Medscape.com.
compared with people without HIV.
A comparison of outcomes of people with HIV to people without HIV who were hospitalized in the United Kingdom with COVID-19 from Jan. 17 to June 4 showed that HIV-positive status was associated with a 63% increased risk of day 28 mortality.
This was especially true for HIV+ patients younger than 70 years of age, said Anna Maria Geretti, MD, PhD, professor of virology and infectious diseases, University of Liverpool, England.
The results are from an analysis of data from the ISARIC World Health Organization (WHO) Clinical Characterisation Protocol (UK) study, and were presented at the HIV Glasgow annual meeting, held virtually this year because of the pandemic.
“We investigated whether HIV status could be important in COVID-19 outcomes because there was anxiety on the part of our patients, and we wanted to gather some evidence-based information in order to help guide them,” Dr. Geretti said in an interview.
“ISARIC is an international protocol and the UK is one of the nations participating. We applied for access to its very large database, which connects data from all patients who are hospitalized with either known or suspected COVID-19. We wanted to see specifically how the presentation and outcomes of patients with HIV compared with the rest of the population without HIV. It afforded us an ideal opportunity to start to answer this question, and this is our first analysis in what will be an ongoing process. Importantly, we showed that there is a need to really look more carefully at the population with HIV,” she said.
Out of a total of 47,539 patients in the database, 115 (0.24%) had confirmed HIV-positive status, and 103 of those 115, or 89.6%, had a record of being on antiretroviral therapy.
On admission, the patients with HIV were younger, with a median age of 55 compared with 74 for patients without HIV (P < .001). They also had a higher prevalence of obesity, moderate to severe liver disease, higher lymphocyte counts and C-reactive protein, as well as more systemic symptoms.
There were no differences in respiratory rate, need for oxygen, or prevalence of chest infiltrates.
The cumulative incidence of mortality at day 28 was 25.2% in HIV-positive patients compared with 32.1% in HIV-negative patients (P = .12).
But when the researchers looked more closely, they noticed that the mortality rate was actually higher in younger HIV+ patients compared with HIV-negative patients.
Stratified by age, 28-day mortality was significantly higher in HIV+ patients aged <50 years (P =.004); and those aged 50 to 59 years (P = .05).
“So below the age of 70, the risk of mortality was double in people with HIV. The people with HIV who died often had diabetes with complications and also more frequent obesity, but this was not the only explanation,” Dr. Geretti said. “There is something to do with the HIV status per se.”
Next steps will be to expand the data set and repeat the analysis with an additional 100 patients “at least” she said.
The researchers also hope to zero in on what about being HIV+ is increasing the mortality risk from COVID-19.
“Right now we need greater numbers and we hope that the research community will be stimulated to take a closer look at this information, and merge other data so that we can strengthen confidence in the data and tease out what factors are causing this increased risk for mortality,” Dr. Geretti said.
She also emphasized that all patients admitted to hospital with COVID-19 should be asked about their HIV status.
“It is important that the HIV status be recorded if we want to increase our ability to understand how HIV impacts survival,” she stressed. “In our experience we found that most of the hospital records were not doing that. Since HIV+ patients seem to be at increased risk, HIV status should be factored into the clinical management. Ask patients if they are HIV+, and if it is not known, then do a test. That would be good practice.”
Dr. Geretti reported no relevant financial relationships. The work was supported by grants from the National Institute of Health Research, the Medical Research Council, the Wellcome Trust, the Department for International Development, and the Bill and Melinda Gates Foundation.
A version of this article originally appeared on Medscape.com.
Switch to integrase inhibitor regimen safe and effective
data from a randomized trial indicate.
Among 212 women with successful HIV virologic suppression following 48 weeks of treatment with ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate (ATV/r +TDF), among those who were switched to continued therapy with an integrase inhibitor–based regimen of elvitegravir/cobicistat/emtricitabine and tenofovir alafenamide (E/C/F/TAF), mean increases in lumbar spine bone mineral density (BMD) were greater and renal function was improved compared with patients who were maintained with ATV/r + TDF, reported Monica Thormann, MD, from Salvador B. Gautier Hospital in Santo Domingo, Dominican Republic, and colleagues at the HIV Glasgow drug therapy meeting, which was held online in 2020.
Although the E/C/F/TAF regimen was associated with a significantly greater increase in lipids, there was no significant change in the total cholesterol to high-density lipoprotein (HDL) cholesterol ratio.
The patients in the study had previously participated in a blinded randomized trial comparing the integrase inhibitor combination plus TDF with ATV/r + TDF in treatment-naive women.
In the current study, patients were randomly assigned in a 3:1 ratio to maintenance with either E/C/F/TAF (159 patients) or ATV/r + TDF (53 patients).
Forty-eight weeks after the switch, virologic suppression (to fewer than 50 copies/mL) was maintained among 94.3% of those on the integrase inhibitor–based regimen, compared with 86.8% of those on the protease inhibitor–based regimen. Virologic failure was seen in 1.9% of those on the integrase inhibitor–based regimen and in 3.8% of those on the protease inhibitor–based regimen.
In addition, virologic suppression below 20 c/mL at week 48 was more common among women maintained on E/C/F/TAF, at 84.9% vs 71.7% (P = .041). No treatment-emergent resistance was seen with either regimen.
As noted, there were higher mean percentage increases in BMD in the E/C/F/TAF group for both total hip and lumbar spine, but only the latter measure improved significantly in comparison with patients treated with ATV/r + TDF (2.82% vs 0%, P < .001).
Markers of renal tubule damage, including the beta-2 microglobulin to creatinine ratio and the rentinol-binding protein to creatinine ratio, were significantly improved with the integrase inhibitor regimen.
Increases in total cholesterol, LDL cholesterol, and HDL cholesterol were 27 vs 5 mg/dL, 16 vs 8 mg/dL, and 5 vs 0 mg/dL in each case comparing the integrase inhibitor–based regimen to the protease inhibitor–based regimen. All of those comparisons were statistically significant.
As noted, however, the total cholesterol to HDL cholesterol ratio was not significantly different between the treatment arms. The rate or initiation of lipid-modifying agents was 1.3% in the E/C/F/TAF group vs 0 in the ATV/r + TDF group, but this difference was not statistically significant.
“These data demonstrate that women who switch to an integrase inhibitor + TAF‐based regimen maintain high levels of virologic suppression with improvement in BMD and renal function biomarkers, as compared with those remaining on their ritonavir boosted atazanavir + TDF‐based regimen,” the authors wrote.
This article first appeared on Medscape.com.
data from a randomized trial indicate.
Among 212 women with successful HIV virologic suppression following 48 weeks of treatment with ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate (ATV/r +TDF), among those who were switched to continued therapy with an integrase inhibitor–based regimen of elvitegravir/cobicistat/emtricitabine and tenofovir alafenamide (E/C/F/TAF), mean increases in lumbar spine bone mineral density (BMD) were greater and renal function was improved compared with patients who were maintained with ATV/r + TDF, reported Monica Thormann, MD, from Salvador B. Gautier Hospital in Santo Domingo, Dominican Republic, and colleagues at the HIV Glasgow drug therapy meeting, which was held online in 2020.
Although the E/C/F/TAF regimen was associated with a significantly greater increase in lipids, there was no significant change in the total cholesterol to high-density lipoprotein (HDL) cholesterol ratio.
The patients in the study had previously participated in a blinded randomized trial comparing the integrase inhibitor combination plus TDF with ATV/r + TDF in treatment-naive women.
In the current study, patients were randomly assigned in a 3:1 ratio to maintenance with either E/C/F/TAF (159 patients) or ATV/r + TDF (53 patients).
Forty-eight weeks after the switch, virologic suppression (to fewer than 50 copies/mL) was maintained among 94.3% of those on the integrase inhibitor–based regimen, compared with 86.8% of those on the protease inhibitor–based regimen. Virologic failure was seen in 1.9% of those on the integrase inhibitor–based regimen and in 3.8% of those on the protease inhibitor–based regimen.
In addition, virologic suppression below 20 c/mL at week 48 was more common among women maintained on E/C/F/TAF, at 84.9% vs 71.7% (P = .041). No treatment-emergent resistance was seen with either regimen.
As noted, there were higher mean percentage increases in BMD in the E/C/F/TAF group for both total hip and lumbar spine, but only the latter measure improved significantly in comparison with patients treated with ATV/r + TDF (2.82% vs 0%, P < .001).
Markers of renal tubule damage, including the beta-2 microglobulin to creatinine ratio and the rentinol-binding protein to creatinine ratio, were significantly improved with the integrase inhibitor regimen.
Increases in total cholesterol, LDL cholesterol, and HDL cholesterol were 27 vs 5 mg/dL, 16 vs 8 mg/dL, and 5 vs 0 mg/dL in each case comparing the integrase inhibitor–based regimen to the protease inhibitor–based regimen. All of those comparisons were statistically significant.
As noted, however, the total cholesterol to HDL cholesterol ratio was not significantly different between the treatment arms. The rate or initiation of lipid-modifying agents was 1.3% in the E/C/F/TAF group vs 0 in the ATV/r + TDF group, but this difference was not statistically significant.
“These data demonstrate that women who switch to an integrase inhibitor + TAF‐based regimen maintain high levels of virologic suppression with improvement in BMD and renal function biomarkers, as compared with those remaining on their ritonavir boosted atazanavir + TDF‐based regimen,” the authors wrote.
This article first appeared on Medscape.com.
data from a randomized trial indicate.
Among 212 women with successful HIV virologic suppression following 48 weeks of treatment with ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate (ATV/r +TDF), among those who were switched to continued therapy with an integrase inhibitor–based regimen of elvitegravir/cobicistat/emtricitabine and tenofovir alafenamide (E/C/F/TAF), mean increases in lumbar spine bone mineral density (BMD) were greater and renal function was improved compared with patients who were maintained with ATV/r + TDF, reported Monica Thormann, MD, from Salvador B. Gautier Hospital in Santo Domingo, Dominican Republic, and colleagues at the HIV Glasgow drug therapy meeting, which was held online in 2020.
Although the E/C/F/TAF regimen was associated with a significantly greater increase in lipids, there was no significant change in the total cholesterol to high-density lipoprotein (HDL) cholesterol ratio.
The patients in the study had previously participated in a blinded randomized trial comparing the integrase inhibitor combination plus TDF with ATV/r + TDF in treatment-naive women.
In the current study, patients were randomly assigned in a 3:1 ratio to maintenance with either E/C/F/TAF (159 patients) or ATV/r + TDF (53 patients).
Forty-eight weeks after the switch, virologic suppression (to fewer than 50 copies/mL) was maintained among 94.3% of those on the integrase inhibitor–based regimen, compared with 86.8% of those on the protease inhibitor–based regimen. Virologic failure was seen in 1.9% of those on the integrase inhibitor–based regimen and in 3.8% of those on the protease inhibitor–based regimen.
In addition, virologic suppression below 20 c/mL at week 48 was more common among women maintained on E/C/F/TAF, at 84.9% vs 71.7% (P = .041). No treatment-emergent resistance was seen with either regimen.
As noted, there were higher mean percentage increases in BMD in the E/C/F/TAF group for both total hip and lumbar spine, but only the latter measure improved significantly in comparison with patients treated with ATV/r + TDF (2.82% vs 0%, P < .001).
Markers of renal tubule damage, including the beta-2 microglobulin to creatinine ratio and the rentinol-binding protein to creatinine ratio, were significantly improved with the integrase inhibitor regimen.
Increases in total cholesterol, LDL cholesterol, and HDL cholesterol were 27 vs 5 mg/dL, 16 vs 8 mg/dL, and 5 vs 0 mg/dL in each case comparing the integrase inhibitor–based regimen to the protease inhibitor–based regimen. All of those comparisons were statistically significant.
As noted, however, the total cholesterol to HDL cholesterol ratio was not significantly different between the treatment arms. The rate or initiation of lipid-modifying agents was 1.3% in the E/C/F/TAF group vs 0 in the ATV/r + TDF group, but this difference was not statistically significant.
“These data demonstrate that women who switch to an integrase inhibitor + TAF‐based regimen maintain high levels of virologic suppression with improvement in BMD and renal function biomarkers, as compared with those remaining on their ritonavir boosted atazanavir + TDF‐based regimen,” the authors wrote.
This article first appeared on Medscape.com.
Delayed cancer screening could cause increase in deaths, study says
Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.
When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.
“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.
Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .
The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.
Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.
The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.
Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.
“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.
United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.
“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
This article first appeared on Medscape.com.
Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.
When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.
“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.
Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .
The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.
Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.
The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.
Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.
“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.
United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.
“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
This article first appeared on Medscape.com.
Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.
When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.
“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.
Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .
The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.
Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.
The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.
Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.
“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.
United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.
“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
This article first appeared on Medscape.com.
Burosumab is a ‘game changer,’ effective in all subgroups of XLH
A recently approved agent, burosumab (Crysvita), was better than placebo across a range of efficacy outcomes for 14 predefined subgroups of adults with X-linked hypophosphatemia (XLH), new research shows.
The authors analyzed data from the initial 24-week randomized blinded phase of the pivotal phase 3 trial that led to regulatory approval of this drug in the United States in 2018 for XLH, a rare form of rickets characterized by low serum phosphorus levels, skeletal defects, pain, and stiffness.
As in the main analysis, in the subgroups, among patients who received burosumab, serum phosphorus levels were improved, and outcomes were better on the following measures: Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness scale, the WOMAC physical function measure, and the Brief Pain Inventory (BPI), which were the main efficacy outcomes. Improvements were seen for many other outcomes as well.
Maria-Luisa Brandi, MD, Careggi University Hospital, Florence, Italy, presented the new subanalysis during the virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting.
The subgroup results were consistent with the overall trial findings, “showing a favorable direction of effect of burosumab relative to placebo” except for results in patients recruited in Asia and non-White patients; those results were considered inconclusive because there were too few participants in those categories, she told Medscape Medical News,.
Lorenz Hofbauer, MD, scientific chair of the ASBMR meeting, said that the take-away message is that the drug “works to reduce pain and disability” in adults with XLH with more severe/less severe symptoms, and “it provides new hope for many patients suffering from this disease,” he told Medscape Medical News.
Burosemab also appears superior to what has previously been considered standard therapy for XLH, phosphate/calcitriol, the experts say.
‘Rare is relative,’ burosumab is a ‘transformative therapy’
“The disease prevalence is 1 to 9 in a million,” Brandi said. “Undiagnosed adults are treated by the doctor that makes the diagnosis, usually a nephrologist or a rheumatologist or a bone doctor; this depends on the prevalent complications in a given patient. The endocrinologist who treats this patient is the one expert in bone disorders.”
Hofbauer noted, however, that “[r]are is relative. If you run a bone clinic, you will see four to five patients with XLH; if you are a regional center, 20 to 30 patients. People with rare disease travel more than 1000 miles to see experts.”
The US Food and Drug Administration approved burosumab for use in children and adults with XLH 2 years ago. The European Medicines Agency (EMA) approved it for use in children.
The drug is expected to be approved by the EMA for adults with XLH some time this year, said Hofbauer, who is from Dresden Technical University, Dresden, Germany.
Burosumab is a “game changer” with respect to previous treatments, he stressed.
This study is one of the top five clinical abstracts of the ASBMR meeting, which are selected on the basis of “scientific content/novelty, making a difference in clinical practice,” Hofbauer explained. He noted that “new drugs that work are always in the top ranks.”
Craig Munns, PhD, who was senior author of a recent review about burosumab, agrees.
“Burosumab is transformative, as it is a paradigm shift in the way we manage XLH,” he told Medscape Medical News.
“Standard therapy for children is with oral phosphate and calcitriol, and many adults do not receive any therapy,” said Munns, from the University of Sydney, Sydney, Australia.
“Phosphate and calcitriol need to be taken multiple times per day, is an incomplete therapy, and has many complications. Burosumab offers a 2-weekly (children) or 4-weekly (adult) dosing regime with superior outcomes compared to no treatment or phosphate/calcitriol,” he emphasized.
Efficacy in 14 predefined subgroups
“Burosumab is an anti-FGF-23 [anti–fibroblast growth factor-23] antibody for a rare genetic disease, XLH, in which the gene for PHEX is defective,” Hofbauer explained.
“PHEX is an enzyme that clears FGF-23; if it does not work, then FGF-23 accumulates in the body and causes phosphate wasting with wide consequences for bone, muscle, and joints. Burosumab is a smart approach, since it blocks these excessive FGF-23 effects.”
Children with XLH have rickets, deformities in the lower skeleton, and short stature, Brandi noted, whereas adults have fractures, pseudofractures, enthesopathy (calcification of joint capsule, tendon insertions, and ligaments), pain, stiffness, and impaired physical function.
However, “treatment with oral phosphate and vitamin D is associated with nephrocalcinosis and hyperparathyroidism,” she said.
In the phase 3 trial, 134 adults (aged 18 to 65 years) with XLH were randomly assigned in a double-blind manner to receive either burosumab or placebo for 24 weeks, followed by 24 weeks of open-label burosumab. The patients’ serum phosphorus levels were <2.5 mg/dL, and they were experiencing measurable bone/joint pain.
Baseline characteristics were similar for the patients who received placebo (66) and those who received burosumab (68). The mean age of the patients was 40 years; 65% were women; and 81% were White.
The current exploratory analysis examined efficacy outcomes in patients grouped according to the following factors and characteristics: sex; age (≤41 years or >41 years); race (non-White, White); region (Asia, North America/Europe); baseline WOMAC pain score; WOMAC total pain; WOMAC stiffness; WOMAC physical function; BPI worst pain; BPI average pain; opioid use; pain medication use; active fractures and pseudofractures; and 6-minute walking test distance.
The efficacy outcomes were as follows: serum phosphorus level (primary outcome), BPI worst pain, WOMAC stiffness, and WOMAC physical function (key secondary outcomes); and WOMAC pain, WOMAC total score, BPI average pain, BPI pain interference, BPI worst fatigue, BPI global score, patient global impression (PGI), and 6-minute walking distance.
In the overall cohort, at 24 weeks, in comparison with patients who received placebo, patients who received burosumab had favorable responses with respect to serum phosphorus level, WOMAC stiffness (P =. 012),WOMAC physical function (P = .048), and BPI worst pain (P = .092, not significant), as well as significant improvements in WOMAC total score and the 6-minute walk test. There were nonsignificant improvements in WOMAC pain and BPI average pain.
In the subgroup analysis, burosumab was superior to placebo for the primary outcome (serum phosphorus) in all subgroups. It was also superior to placebo for the key secondary outcomes (worst pain, stiffness, and physical function) across all subgroups except for patients from Asia (18 patients) and non-White patients (26).
The study was funded by Kyowa Kirin in partnership with Ultragenyx. Brandi receives consultancy and speaker fees as well as research grants from Kyowa Kirin and other pharmaceutical companies. Munns has received research funding from Kyowa Kirin.
This article first appeared on Medscape.com.
A recently approved agent, burosumab (Crysvita), was better than placebo across a range of efficacy outcomes for 14 predefined subgroups of adults with X-linked hypophosphatemia (XLH), new research shows.
The authors analyzed data from the initial 24-week randomized blinded phase of the pivotal phase 3 trial that led to regulatory approval of this drug in the United States in 2018 for XLH, a rare form of rickets characterized by low serum phosphorus levels, skeletal defects, pain, and stiffness.
As in the main analysis, in the subgroups, among patients who received burosumab, serum phosphorus levels were improved, and outcomes were better on the following measures: Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness scale, the WOMAC physical function measure, and the Brief Pain Inventory (BPI), which were the main efficacy outcomes. Improvements were seen for many other outcomes as well.
Maria-Luisa Brandi, MD, Careggi University Hospital, Florence, Italy, presented the new subanalysis during the virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting.
The subgroup results were consistent with the overall trial findings, “showing a favorable direction of effect of burosumab relative to placebo” except for results in patients recruited in Asia and non-White patients; those results were considered inconclusive because there were too few participants in those categories, she told Medscape Medical News,.
Lorenz Hofbauer, MD, scientific chair of the ASBMR meeting, said that the take-away message is that the drug “works to reduce pain and disability” in adults with XLH with more severe/less severe symptoms, and “it provides new hope for many patients suffering from this disease,” he told Medscape Medical News.
Burosemab also appears superior to what has previously been considered standard therapy for XLH, phosphate/calcitriol, the experts say.
‘Rare is relative,’ burosumab is a ‘transformative therapy’
“The disease prevalence is 1 to 9 in a million,” Brandi said. “Undiagnosed adults are treated by the doctor that makes the diagnosis, usually a nephrologist or a rheumatologist or a bone doctor; this depends on the prevalent complications in a given patient. The endocrinologist who treats this patient is the one expert in bone disorders.”
Hofbauer noted, however, that “[r]are is relative. If you run a bone clinic, you will see four to five patients with XLH; if you are a regional center, 20 to 30 patients. People with rare disease travel more than 1000 miles to see experts.”
The US Food and Drug Administration approved burosumab for use in children and adults with XLH 2 years ago. The European Medicines Agency (EMA) approved it for use in children.
The drug is expected to be approved by the EMA for adults with XLH some time this year, said Hofbauer, who is from Dresden Technical University, Dresden, Germany.
Burosumab is a “game changer” with respect to previous treatments, he stressed.
This study is one of the top five clinical abstracts of the ASBMR meeting, which are selected on the basis of “scientific content/novelty, making a difference in clinical practice,” Hofbauer explained. He noted that “new drugs that work are always in the top ranks.”
Craig Munns, PhD, who was senior author of a recent review about burosumab, agrees.
“Burosumab is transformative, as it is a paradigm shift in the way we manage XLH,” he told Medscape Medical News.
“Standard therapy for children is with oral phosphate and calcitriol, and many adults do not receive any therapy,” said Munns, from the University of Sydney, Sydney, Australia.
“Phosphate and calcitriol need to be taken multiple times per day, is an incomplete therapy, and has many complications. Burosumab offers a 2-weekly (children) or 4-weekly (adult) dosing regime with superior outcomes compared to no treatment or phosphate/calcitriol,” he emphasized.
Efficacy in 14 predefined subgroups
“Burosumab is an anti-FGF-23 [anti–fibroblast growth factor-23] antibody for a rare genetic disease, XLH, in which the gene for PHEX is defective,” Hofbauer explained.
“PHEX is an enzyme that clears FGF-23; if it does not work, then FGF-23 accumulates in the body and causes phosphate wasting with wide consequences for bone, muscle, and joints. Burosumab is a smart approach, since it blocks these excessive FGF-23 effects.”
Children with XLH have rickets, deformities in the lower skeleton, and short stature, Brandi noted, whereas adults have fractures, pseudofractures, enthesopathy (calcification of joint capsule, tendon insertions, and ligaments), pain, stiffness, and impaired physical function.
However, “treatment with oral phosphate and vitamin D is associated with nephrocalcinosis and hyperparathyroidism,” she said.
In the phase 3 trial, 134 adults (aged 18 to 65 years) with XLH were randomly assigned in a double-blind manner to receive either burosumab or placebo for 24 weeks, followed by 24 weeks of open-label burosumab. The patients’ serum phosphorus levels were <2.5 mg/dL, and they were experiencing measurable bone/joint pain.
Baseline characteristics were similar for the patients who received placebo (66) and those who received burosumab (68). The mean age of the patients was 40 years; 65% were women; and 81% were White.
The current exploratory analysis examined efficacy outcomes in patients grouped according to the following factors and characteristics: sex; age (≤41 years or >41 years); race (non-White, White); region (Asia, North America/Europe); baseline WOMAC pain score; WOMAC total pain; WOMAC stiffness; WOMAC physical function; BPI worst pain; BPI average pain; opioid use; pain medication use; active fractures and pseudofractures; and 6-minute walking test distance.
The efficacy outcomes were as follows: serum phosphorus level (primary outcome), BPI worst pain, WOMAC stiffness, and WOMAC physical function (key secondary outcomes); and WOMAC pain, WOMAC total score, BPI average pain, BPI pain interference, BPI worst fatigue, BPI global score, patient global impression (PGI), and 6-minute walking distance.
In the overall cohort, at 24 weeks, in comparison with patients who received placebo, patients who received burosumab had favorable responses with respect to serum phosphorus level, WOMAC stiffness (P =. 012),WOMAC physical function (P = .048), and BPI worst pain (P = .092, not significant), as well as significant improvements in WOMAC total score and the 6-minute walk test. There were nonsignificant improvements in WOMAC pain and BPI average pain.
In the subgroup analysis, burosumab was superior to placebo for the primary outcome (serum phosphorus) in all subgroups. It was also superior to placebo for the key secondary outcomes (worst pain, stiffness, and physical function) across all subgroups except for patients from Asia (18 patients) and non-White patients (26).
The study was funded by Kyowa Kirin in partnership with Ultragenyx. Brandi receives consultancy and speaker fees as well as research grants from Kyowa Kirin and other pharmaceutical companies. Munns has received research funding from Kyowa Kirin.
This article first appeared on Medscape.com.
A recently approved agent, burosumab (Crysvita), was better than placebo across a range of efficacy outcomes for 14 predefined subgroups of adults with X-linked hypophosphatemia (XLH), new research shows.
The authors analyzed data from the initial 24-week randomized blinded phase of the pivotal phase 3 trial that led to regulatory approval of this drug in the United States in 2018 for XLH, a rare form of rickets characterized by low serum phosphorus levels, skeletal defects, pain, and stiffness.
As in the main analysis, in the subgroups, among patients who received burosumab, serum phosphorus levels were improved, and outcomes were better on the following measures: Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness scale, the WOMAC physical function measure, and the Brief Pain Inventory (BPI), which were the main efficacy outcomes. Improvements were seen for many other outcomes as well.
Maria-Luisa Brandi, MD, Careggi University Hospital, Florence, Italy, presented the new subanalysis during the virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting.
The subgroup results were consistent with the overall trial findings, “showing a favorable direction of effect of burosumab relative to placebo” except for results in patients recruited in Asia and non-White patients; those results were considered inconclusive because there were too few participants in those categories, she told Medscape Medical News,.
Lorenz Hofbauer, MD, scientific chair of the ASBMR meeting, said that the take-away message is that the drug “works to reduce pain and disability” in adults with XLH with more severe/less severe symptoms, and “it provides new hope for many patients suffering from this disease,” he told Medscape Medical News.
Burosemab also appears superior to what has previously been considered standard therapy for XLH, phosphate/calcitriol, the experts say.
‘Rare is relative,’ burosumab is a ‘transformative therapy’
“The disease prevalence is 1 to 9 in a million,” Brandi said. “Undiagnosed adults are treated by the doctor that makes the diagnosis, usually a nephrologist or a rheumatologist or a bone doctor; this depends on the prevalent complications in a given patient. The endocrinologist who treats this patient is the one expert in bone disorders.”
Hofbauer noted, however, that “[r]are is relative. If you run a bone clinic, you will see four to five patients with XLH; if you are a regional center, 20 to 30 patients. People with rare disease travel more than 1000 miles to see experts.”
The US Food and Drug Administration approved burosumab for use in children and adults with XLH 2 years ago. The European Medicines Agency (EMA) approved it for use in children.
The drug is expected to be approved by the EMA for adults with XLH some time this year, said Hofbauer, who is from Dresden Technical University, Dresden, Germany.
Burosumab is a “game changer” with respect to previous treatments, he stressed.
This study is one of the top five clinical abstracts of the ASBMR meeting, which are selected on the basis of “scientific content/novelty, making a difference in clinical practice,” Hofbauer explained. He noted that “new drugs that work are always in the top ranks.”
Craig Munns, PhD, who was senior author of a recent review about burosumab, agrees.
“Burosumab is transformative, as it is a paradigm shift in the way we manage XLH,” he told Medscape Medical News.
“Standard therapy for children is with oral phosphate and calcitriol, and many adults do not receive any therapy,” said Munns, from the University of Sydney, Sydney, Australia.
“Phosphate and calcitriol need to be taken multiple times per day, is an incomplete therapy, and has many complications. Burosumab offers a 2-weekly (children) or 4-weekly (adult) dosing regime with superior outcomes compared to no treatment or phosphate/calcitriol,” he emphasized.
Efficacy in 14 predefined subgroups
“Burosumab is an anti-FGF-23 [anti–fibroblast growth factor-23] antibody for a rare genetic disease, XLH, in which the gene for PHEX is defective,” Hofbauer explained.
“PHEX is an enzyme that clears FGF-23; if it does not work, then FGF-23 accumulates in the body and causes phosphate wasting with wide consequences for bone, muscle, and joints. Burosumab is a smart approach, since it blocks these excessive FGF-23 effects.”
Children with XLH have rickets, deformities in the lower skeleton, and short stature, Brandi noted, whereas adults have fractures, pseudofractures, enthesopathy (calcification of joint capsule, tendon insertions, and ligaments), pain, stiffness, and impaired physical function.
However, “treatment with oral phosphate and vitamin D is associated with nephrocalcinosis and hyperparathyroidism,” she said.
In the phase 3 trial, 134 adults (aged 18 to 65 years) with XLH were randomly assigned in a double-blind manner to receive either burosumab or placebo for 24 weeks, followed by 24 weeks of open-label burosumab. The patients’ serum phosphorus levels were <2.5 mg/dL, and they were experiencing measurable bone/joint pain.
Baseline characteristics were similar for the patients who received placebo (66) and those who received burosumab (68). The mean age of the patients was 40 years; 65% were women; and 81% were White.
The current exploratory analysis examined efficacy outcomes in patients grouped according to the following factors and characteristics: sex; age (≤41 years or >41 years); race (non-White, White); region (Asia, North America/Europe); baseline WOMAC pain score; WOMAC total pain; WOMAC stiffness; WOMAC physical function; BPI worst pain; BPI average pain; opioid use; pain medication use; active fractures and pseudofractures; and 6-minute walking test distance.
The efficacy outcomes were as follows: serum phosphorus level (primary outcome), BPI worst pain, WOMAC stiffness, and WOMAC physical function (key secondary outcomes); and WOMAC pain, WOMAC total score, BPI average pain, BPI pain interference, BPI worst fatigue, BPI global score, patient global impression (PGI), and 6-minute walking distance.
In the overall cohort, at 24 weeks, in comparison with patients who received placebo, patients who received burosumab had favorable responses with respect to serum phosphorus level, WOMAC stiffness (P =. 012),WOMAC physical function (P = .048), and BPI worst pain (P = .092, not significant), as well as significant improvements in WOMAC total score and the 6-minute walk test. There were nonsignificant improvements in WOMAC pain and BPI average pain.
In the subgroup analysis, burosumab was superior to placebo for the primary outcome (serum phosphorus) in all subgroups. It was also superior to placebo for the key secondary outcomes (worst pain, stiffness, and physical function) across all subgroups except for patients from Asia (18 patients) and non-White patients (26).
The study was funded by Kyowa Kirin in partnership with Ultragenyx. Brandi receives consultancy and speaker fees as well as research grants from Kyowa Kirin and other pharmaceutical companies. Munns has received research funding from Kyowa Kirin.
This article first appeared on Medscape.com.
Islatravir + doravirine maintains HIV viral suppression
according to new data.
ISL is a first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTTI), Jean-Michel Molina, MD, PhD, of Saint‐Louis and Lariboisière Hospitals in Paris, explained at the annual HIV drug therapy meeting in Glasgow, Scotland. The randomized, double-blind, dose‐ranging trial compared ISL+DOR to a fixed‐dose combination of DOR, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF) daily in 121 patients.
Patients in the ISL+DOR group initially received 0.25, 0.75, or 2.25 mg of ISL along with 100 mg of DOR and 200 mg of 3TC. Beginning at week 20, participants achieving HIV viral loads of 50 copies/mL or less discontinued 3TC but continued on their assigned dose of ISL+DOR for at least 24 weeks. At that point the investigators noted a greater number of discontinuations in the 2.25-mg group and settled on the 0.75-mg ISL dose. All patients in the ISL group were transitioned to that dose between weeks 60 and 72.
At week 96, 81.1% of the patients in the combined ISL group maintained viral loads <50 copies/mL, comparable to the 80.6% of those in the DOR/3TC/TDF group.
ISL+DOR appeared to be “well tolerated,” the investigators noted. They found drug-related adverse events in 7.8% of the patients in the ISL+DOR group compared with 22.6% of patients in the DOR/3TC/TDF group. In addition, among the 90 patients in the ISL+DOR group, no more than 5% of participants experienced any specific drug-related adverse event.
Source: HIV Glasgow 2020 Virtual Conference: Abstract O415. Oct. 5-8, 2020.
A version of this article originally appeared on Medscape.com.
according to new data.
ISL is a first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTTI), Jean-Michel Molina, MD, PhD, of Saint‐Louis and Lariboisière Hospitals in Paris, explained at the annual HIV drug therapy meeting in Glasgow, Scotland. The randomized, double-blind, dose‐ranging trial compared ISL+DOR to a fixed‐dose combination of DOR, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF) daily in 121 patients.
Patients in the ISL+DOR group initially received 0.25, 0.75, or 2.25 mg of ISL along with 100 mg of DOR and 200 mg of 3TC. Beginning at week 20, participants achieving HIV viral loads of 50 copies/mL or less discontinued 3TC but continued on their assigned dose of ISL+DOR for at least 24 weeks. At that point the investigators noted a greater number of discontinuations in the 2.25-mg group and settled on the 0.75-mg ISL dose. All patients in the ISL group were transitioned to that dose between weeks 60 and 72.
At week 96, 81.1% of the patients in the combined ISL group maintained viral loads <50 copies/mL, comparable to the 80.6% of those in the DOR/3TC/TDF group.
ISL+DOR appeared to be “well tolerated,” the investigators noted. They found drug-related adverse events in 7.8% of the patients in the ISL+DOR group compared with 22.6% of patients in the DOR/3TC/TDF group. In addition, among the 90 patients in the ISL+DOR group, no more than 5% of participants experienced any specific drug-related adverse event.
Source: HIV Glasgow 2020 Virtual Conference: Abstract O415. Oct. 5-8, 2020.
A version of this article originally appeared on Medscape.com.
according to new data.
ISL is a first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTTI), Jean-Michel Molina, MD, PhD, of Saint‐Louis and Lariboisière Hospitals in Paris, explained at the annual HIV drug therapy meeting in Glasgow, Scotland. The randomized, double-blind, dose‐ranging trial compared ISL+DOR to a fixed‐dose combination of DOR, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF) daily in 121 patients.
Patients in the ISL+DOR group initially received 0.25, 0.75, or 2.25 mg of ISL along with 100 mg of DOR and 200 mg of 3TC. Beginning at week 20, participants achieving HIV viral loads of 50 copies/mL or less discontinued 3TC but continued on their assigned dose of ISL+DOR for at least 24 weeks. At that point the investigators noted a greater number of discontinuations in the 2.25-mg group and settled on the 0.75-mg ISL dose. All patients in the ISL group were transitioned to that dose between weeks 60 and 72.
At week 96, 81.1% of the patients in the combined ISL group maintained viral loads <50 copies/mL, comparable to the 80.6% of those in the DOR/3TC/TDF group.
ISL+DOR appeared to be “well tolerated,” the investigators noted. They found drug-related adverse events in 7.8% of the patients in the ISL+DOR group compared with 22.6% of patients in the DOR/3TC/TDF group. In addition, among the 90 patients in the ISL+DOR group, no more than 5% of participants experienced any specific drug-related adverse event.
Source: HIV Glasgow 2020 Virtual Conference: Abstract O415. Oct. 5-8, 2020.
A version of this article originally appeared on Medscape.com.
Intensive surveillance after CRC resection does not improve survival
However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.
In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).
Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.
However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”
Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.
He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.
Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”
Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
Study details
The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.
PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.
Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.
Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.
At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
Results
The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).
There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.
There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).
The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.
The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.
The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.
SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.
However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.
In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).
Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.
However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”
Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.
He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.
Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”
Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
Study details
The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.
PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.
Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.
Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.
At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
Results
The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).
There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.
There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).
The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.
The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.
The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.
SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.
However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.
In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).
Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.
However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”
Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.
He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.
Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”
Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
Study details
The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.
PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.
Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.
Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.
At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
Results
The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).
There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.
There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).
The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.
The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.
The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.
SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.
FROM ESMO 2020
Highlights on Treatment of Progressive MS From ECTRIMS 2020
Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).
The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.
Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.
Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.
Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.
Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.
Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).
The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.
Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.
Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.
Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.
Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.
Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).
The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.
Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.
Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.
Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.
Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.
T2D treatments create tension between glycemic and cardiovascular goals
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
FROM EASD 2020