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European Medicines Agency recommends CAR T-cell approvals
The European Medicines Agency (EMA) has recommended a handful of hematology medications for approval, including two chimeric antigen receptor (CAR) T-cell therapies.
All of the drugs must next be approved by the European Commission in order to be marketed to patients throughout Europe.
At the end of June, the EMA’s Committee for Medicinal Products for Human Use tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta).
The EMA approval recommendations come with risk management measures to address the potential for cytokine release syndrome with both of these treatments. Drug makers must use a patient registry to monitor the long-term safety and efficacy of the therapies.
The EMA is also recommending approval of caplacizumab for acquired thrombotic thrombocytopenic purpura, vonicog alfa for the treatment of von Willebrand disease, and daunorubicin/cytarabine for the treatment of acute myeloid leukemia.
The European Medicines Agency (EMA) has recommended a handful of hematology medications for approval, including two chimeric antigen receptor (CAR) T-cell therapies.
All of the drugs must next be approved by the European Commission in order to be marketed to patients throughout Europe.
At the end of June, the EMA’s Committee for Medicinal Products for Human Use tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta).
The EMA approval recommendations come with risk management measures to address the potential for cytokine release syndrome with both of these treatments. Drug makers must use a patient registry to monitor the long-term safety and efficacy of the therapies.
The EMA is also recommending approval of caplacizumab for acquired thrombotic thrombocytopenic purpura, vonicog alfa for the treatment of von Willebrand disease, and daunorubicin/cytarabine for the treatment of acute myeloid leukemia.
The European Medicines Agency (EMA) has recommended a handful of hematology medications for approval, including two chimeric antigen receptor (CAR) T-cell therapies.
All of the drugs must next be approved by the European Commission in order to be marketed to patients throughout Europe.
At the end of June, the EMA’s Committee for Medicinal Products for Human Use tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta).
The EMA approval recommendations come with risk management measures to address the potential for cytokine release syndrome with both of these treatments. Drug makers must use a patient registry to monitor the long-term safety and efficacy of the therapies.
The EMA is also recommending approval of caplacizumab for acquired thrombotic thrombocytopenic purpura, vonicog alfa for the treatment of von Willebrand disease, and daunorubicin/cytarabine for the treatment of acute myeloid leukemia.
Bortezomib plus vorinostat shows modest response in MCL
but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).
Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.
The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.
From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.
“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”
The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.
SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.
but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).
Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.
The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.
From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.
“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”
The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.
SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.
but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).
Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.
The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.
From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.
“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”
The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.
SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.
FROM CLINICAL LYMPHOMA, MYELOMA AND LEUKEMIA
Antidrug vaccines: A shot in the arm against addiction?
SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.
And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.
For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.
In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.
Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?
Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.
We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.
Q: How are these vaccines expected to work?
A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.
Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?
A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.
Q: How often would people be vaccinated?
A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.
Q: Where does your research stand now?
A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.
SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.
And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.
For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.
In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.
Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?
Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.
We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.
Q: How are these vaccines expected to work?
A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.
Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?
A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.
Q: How often would people be vaccinated?
A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.
Q: Where does your research stand now?
A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.
SAN DIEGO – Heroin, methamphetamine, and cocaine might not seem to have much in common with germs, but chemist Kim D. Janda, PhD, and his colleagues are trying to trick the human body into looking at them the same way: As invaders who must be conquered.
And what’s the best way to prepare the immune system for a fight? Train it through vaccination – the key to so many victories over viruses and bacteria.
For decades now, Dr. Janda, of the Scripps Research Institute in La Jolla, Calif., and other scientists have tried to develop a vaccine that would blunt the effects of substances of abuse, such as illicit drugs and even tobacco. The idea is to arm the immune system with antibodies that will prevent some or all drug components from breaking through the blood-brain barrier and producing psychoactive reactions.
In a follow-up interview after his presentation at the annual meeting of the College on Problems of Drug Dependence, Dr. Janda spoke about the history of research in this area, the potential workings of a vaccine, and the challenges of moving his own research forward.
Question: What’s the history of scientists’ efforts to develop a vaccine against drugs of abuse?
Answer: People looked at it back in the 1970s, but it didn’t really pan out. It was pretty dormant until we published research about a cocaine vaccine in 1995.
We worked on that for a while, then we looked at methamphetamine, Rohypnol, and opioids. There have been clinical trials for nicotine and cocaine, but they’ve failed.
Q: How are these vaccines expected to work?
A: The idea of the vaccines is that you don’t get high, so you won’t feel the effect of the drugs. They’ll never reach the pleasure centers that they’re supposed to.
Q: Is the idea that everyone would get a vaccine against, say, cocaine or heroin, like we routinely get vaccines against various diseases?
A: For an infectious disease like measles or mumps, you give vaccinations, and herd immunity develops. That’s not the case here. These work in a different manner, and they’re not going to be useful for people who don’t want to get off the drug. Instead, they’re going to be useful for people who want to obtain sobriety. If someone has a weak moment and tries to take the drug to get high, this would hopefully stop that from happening. It could also help overdoses in some cases, since you’re not getting that much drug into the central nervous system where it can cause cardiac arrest.
Q: How often would people be vaccinated?
A: These are vaccines that will be on board for a certain amount of time. We envision 3-4 shots over a 3-month period. You’d come back once a month for 3 months, and you’d be good for maybe 4-6 months.
Q: Where does your research stand now?
A: We’ve made a lot of advances with the opioids, and they’re good enough to put a vaccine in the clinic. Money is the issue. It’s always the issue. But we have to get up to the plate and take our swings – and find if we’ll strike out or get a hit.
REPORTING FROM CPDD 2018
High RA biologic drug levels linked with more infections
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point:
Major finding: High serum levels of a biologic drug were linked with a 51% higher infection rate, compared with those who had normal or low levels.
Study details: Prospective data collected from 703 patients throughout the United Kingdom.
Disclosures: Dr. Jani had no relevant disclosures. Dr. Isaacs has been a consultant to several companies that market biologic drugs for treating rheumatoid arthritis.
Source: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
What to do if you encounter Candida auris
Closely monitor patients for treatment failure
Candida auris is an emerging, often multidrug-resistant yeast that causes invasive infections (such as bloodstream, intra-abdominal) and is transmitted in health care settings. It is difficult to diagnose using traditional yeast identification methods. C. auris also has been found in noninvasive body sites and can colonize a person without causing active infection and hence permitting transmission of the pathogen between patients. These sites include skin, urine, external ear, wounds, and respiratory specimens.
This fungus was first described in 2009 in an ear-discharge culture from a patient in Japan. The first clinical cases were described in South Korea in 2011. An unknown pathogen before 2009, C. auris caused 4%-8% of candidemia in Indian ICUs during 2011-2012 and 38% of candidemia in one Kenyan hospital during 2010-2013. It has now spread across Asia and Europe, only to arrive in the United States in 2016.
As of Aug. 31, 2017, a total of 153 clinical cases of C. auris infection have been reported to CDC from 10 U.S. states; most have occurred in New York and New Jersey. An additional 143 patients have been found to be colonized with C. auris. Based on epidemiologic and molecular information, including whole genome sequencing, the Centers for Disease Control and Prevention infers that most U.S. cases likely resulted from local transmission of C. auris following previous introduction from other countries in Asia.
The majority of infections within the United States have been in blood streams. The reported all-cause mortality from these infections has been up to 60%. Most C. auris isolates in the United States have been resistant to at least one antifungal, most commonly fluconazole, and patients have developed resistance to echinocandin drugs while on treatment. Amphotericin B resistance also has been seen in about 30% of isolates.
In response to global reports and a large outbreak in a specialty hospital in the United Kingdom, the CDC issued its first advisory and clinical alert to health care facilities in June 2016. It is essential for hospitalist physicians to be aware of this emerging pathogen and also of the interventions needed to curb its spread, given they are the frontline warriors in the fight against hospital-acquired infections.
The first step in controlling C. auris is identification. C. auris can be misidentified when using traditional biochemical methods. They are most commonly misidentified as Candida haemulonii. Currently, accurate identification for C. auris can be performed by Vitek MS and matrix-assisted laser desorption/ionization time-of-flight using research use–only databases. Hospitalists should be aware of the diagnostic instruments used in their hospital laboratories and their ability to detect C. auris. Clinical laboratories should request testing of suspect C. auris isolates from their state or regional public health laboratory or the CDC. Laboratories should also consider reviewing historical microbiology records for suspect isolates (e.g., C. haemulonii) to identify missed cases of C. auris.
All cultures positive for Candida should be further speciated and antifungal susceptibilities should be reported as per new Infectious Diseases Society of America guidelines for candidiasis from 2016. As many clinical laboratories do not determine the species of Candida from noninvasive sites, C. auris colonization may go unrecognized and lead to transmission. About 54% of recognized U.S. clinical cases have been identified from blood cultures. The remaining patients with positive C. auris cultures, including those with recent hospitalizations abroad, have had the organism isolated from other body sites, including skin wounds, urine, respiratory specimens, bile fluid, and ears. Determining the species of Candida for isolates from these noninvasive sites in certain situations may allow for more rapid identification of C. auris and allow for timely implementation of targeted infection control measures to reduce transmission.
Patients have been persistently colonized with C. auris, posing long-term risk of transmission. Currently, data on effective decolonization methods are lacking. Patients with suspected or confirmed C. auris infection should be placed in a single room if possible and standard and contact precautions should be initiated and thorough environmental cleaning and disinfection of the patient care area should be undertaken. Using an Environmental Protection Agency–registered antimicrobial product active against Clostridium difficile for routine and terminal disinfection is recommended.
Implement contact tracing and testing to identify other patients colonized with C. auris. Review past microbiology records (at least for the preceding 1 year) for suspect or confirmed cases of C. auris at the institution. Set up enhanced surveillance for C. auris in the laboratory setting.
Echinocandin drugs are the first-line treatment for most invasive Candida infections, making resistance to this class of antifungal drugs particularly concerning. As of Sept. 15, 2017, at least five patients in the United States had echinocandin-resistant isolates. In one patient, resistance to echinocandin drugs developed while being treated with echinocandins.
Based on these findings, CDC is concerned that echinocandin-resistant C. auris could become more common. Patients with C. auris infection should be closely monitored for treatment failure, as indicated by persistently positive clinical cultures (lasting more than 5 days). Consultation with an infectious disease specialist is highly recommended.
Dr. Tirupathi is medical director, infectious diseases/HIV at Keystone Health, and chair, infection prevention, at Summit Health, both in Chambersburg, Pa. He is clinical assistant professor of medicine at Penn State University, Hershey.
Closely monitor patients for treatment failure
Closely monitor patients for treatment failure
Candida auris is an emerging, often multidrug-resistant yeast that causes invasive infections (such as bloodstream, intra-abdominal) and is transmitted in health care settings. It is difficult to diagnose using traditional yeast identification methods. C. auris also has been found in noninvasive body sites and can colonize a person without causing active infection and hence permitting transmission of the pathogen between patients. These sites include skin, urine, external ear, wounds, and respiratory specimens.
This fungus was first described in 2009 in an ear-discharge culture from a patient in Japan. The first clinical cases were described in South Korea in 2011. An unknown pathogen before 2009, C. auris caused 4%-8% of candidemia in Indian ICUs during 2011-2012 and 38% of candidemia in one Kenyan hospital during 2010-2013. It has now spread across Asia and Europe, only to arrive in the United States in 2016.
As of Aug. 31, 2017, a total of 153 clinical cases of C. auris infection have been reported to CDC from 10 U.S. states; most have occurred in New York and New Jersey. An additional 143 patients have been found to be colonized with C. auris. Based on epidemiologic and molecular information, including whole genome sequencing, the Centers for Disease Control and Prevention infers that most U.S. cases likely resulted from local transmission of C. auris following previous introduction from other countries in Asia.
The majority of infections within the United States have been in blood streams. The reported all-cause mortality from these infections has been up to 60%. Most C. auris isolates in the United States have been resistant to at least one antifungal, most commonly fluconazole, and patients have developed resistance to echinocandin drugs while on treatment. Amphotericin B resistance also has been seen in about 30% of isolates.
In response to global reports and a large outbreak in a specialty hospital in the United Kingdom, the CDC issued its first advisory and clinical alert to health care facilities in June 2016. It is essential for hospitalist physicians to be aware of this emerging pathogen and also of the interventions needed to curb its spread, given they are the frontline warriors in the fight against hospital-acquired infections.
The first step in controlling C. auris is identification. C. auris can be misidentified when using traditional biochemical methods. They are most commonly misidentified as Candida haemulonii. Currently, accurate identification for C. auris can be performed by Vitek MS and matrix-assisted laser desorption/ionization time-of-flight using research use–only databases. Hospitalists should be aware of the diagnostic instruments used in their hospital laboratories and their ability to detect C. auris. Clinical laboratories should request testing of suspect C. auris isolates from their state or regional public health laboratory or the CDC. Laboratories should also consider reviewing historical microbiology records for suspect isolates (e.g., C. haemulonii) to identify missed cases of C. auris.
All cultures positive for Candida should be further speciated and antifungal susceptibilities should be reported as per new Infectious Diseases Society of America guidelines for candidiasis from 2016. As many clinical laboratories do not determine the species of Candida from noninvasive sites, C. auris colonization may go unrecognized and lead to transmission. About 54% of recognized U.S. clinical cases have been identified from blood cultures. The remaining patients with positive C. auris cultures, including those with recent hospitalizations abroad, have had the organism isolated from other body sites, including skin wounds, urine, respiratory specimens, bile fluid, and ears. Determining the species of Candida for isolates from these noninvasive sites in certain situations may allow for more rapid identification of C. auris and allow for timely implementation of targeted infection control measures to reduce transmission.
Patients have been persistently colonized with C. auris, posing long-term risk of transmission. Currently, data on effective decolonization methods are lacking. Patients with suspected or confirmed C. auris infection should be placed in a single room if possible and standard and contact precautions should be initiated and thorough environmental cleaning and disinfection of the patient care area should be undertaken. Using an Environmental Protection Agency–registered antimicrobial product active against Clostridium difficile for routine and terminal disinfection is recommended.
Implement contact tracing and testing to identify other patients colonized with C. auris. Review past microbiology records (at least for the preceding 1 year) for suspect or confirmed cases of C. auris at the institution. Set up enhanced surveillance for C. auris in the laboratory setting.
Echinocandin drugs are the first-line treatment for most invasive Candida infections, making resistance to this class of antifungal drugs particularly concerning. As of Sept. 15, 2017, at least five patients in the United States had echinocandin-resistant isolates. In one patient, resistance to echinocandin drugs developed while being treated with echinocandins.
Based on these findings, CDC is concerned that echinocandin-resistant C. auris could become more common. Patients with C. auris infection should be closely monitored for treatment failure, as indicated by persistently positive clinical cultures (lasting more than 5 days). Consultation with an infectious disease specialist is highly recommended.
Dr. Tirupathi is medical director, infectious diseases/HIV at Keystone Health, and chair, infection prevention, at Summit Health, both in Chambersburg, Pa. He is clinical assistant professor of medicine at Penn State University, Hershey.
Candida auris is an emerging, often multidrug-resistant yeast that causes invasive infections (such as bloodstream, intra-abdominal) and is transmitted in health care settings. It is difficult to diagnose using traditional yeast identification methods. C. auris also has been found in noninvasive body sites and can colonize a person without causing active infection and hence permitting transmission of the pathogen between patients. These sites include skin, urine, external ear, wounds, and respiratory specimens.
This fungus was first described in 2009 in an ear-discharge culture from a patient in Japan. The first clinical cases were described in South Korea in 2011. An unknown pathogen before 2009, C. auris caused 4%-8% of candidemia in Indian ICUs during 2011-2012 and 38% of candidemia in one Kenyan hospital during 2010-2013. It has now spread across Asia and Europe, only to arrive in the United States in 2016.
As of Aug. 31, 2017, a total of 153 clinical cases of C. auris infection have been reported to CDC from 10 U.S. states; most have occurred in New York and New Jersey. An additional 143 patients have been found to be colonized with C. auris. Based on epidemiologic and molecular information, including whole genome sequencing, the Centers for Disease Control and Prevention infers that most U.S. cases likely resulted from local transmission of C. auris following previous introduction from other countries in Asia.
The majority of infections within the United States have been in blood streams. The reported all-cause mortality from these infections has been up to 60%. Most C. auris isolates in the United States have been resistant to at least one antifungal, most commonly fluconazole, and patients have developed resistance to echinocandin drugs while on treatment. Amphotericin B resistance also has been seen in about 30% of isolates.
In response to global reports and a large outbreak in a specialty hospital in the United Kingdom, the CDC issued its first advisory and clinical alert to health care facilities in June 2016. It is essential for hospitalist physicians to be aware of this emerging pathogen and also of the interventions needed to curb its spread, given they are the frontline warriors in the fight against hospital-acquired infections.
The first step in controlling C. auris is identification. C. auris can be misidentified when using traditional biochemical methods. They are most commonly misidentified as Candida haemulonii. Currently, accurate identification for C. auris can be performed by Vitek MS and matrix-assisted laser desorption/ionization time-of-flight using research use–only databases. Hospitalists should be aware of the diagnostic instruments used in their hospital laboratories and their ability to detect C. auris. Clinical laboratories should request testing of suspect C. auris isolates from their state or regional public health laboratory or the CDC. Laboratories should also consider reviewing historical microbiology records for suspect isolates (e.g., C. haemulonii) to identify missed cases of C. auris.
All cultures positive for Candida should be further speciated and antifungal susceptibilities should be reported as per new Infectious Diseases Society of America guidelines for candidiasis from 2016. As many clinical laboratories do not determine the species of Candida from noninvasive sites, C. auris colonization may go unrecognized and lead to transmission. About 54% of recognized U.S. clinical cases have been identified from blood cultures. The remaining patients with positive C. auris cultures, including those with recent hospitalizations abroad, have had the organism isolated from other body sites, including skin wounds, urine, respiratory specimens, bile fluid, and ears. Determining the species of Candida for isolates from these noninvasive sites in certain situations may allow for more rapid identification of C. auris and allow for timely implementation of targeted infection control measures to reduce transmission.
Patients have been persistently colonized with C. auris, posing long-term risk of transmission. Currently, data on effective decolonization methods are lacking. Patients with suspected or confirmed C. auris infection should be placed in a single room if possible and standard and contact precautions should be initiated and thorough environmental cleaning and disinfection of the patient care area should be undertaken. Using an Environmental Protection Agency–registered antimicrobial product active against Clostridium difficile for routine and terminal disinfection is recommended.
Implement contact tracing and testing to identify other patients colonized with C. auris. Review past microbiology records (at least for the preceding 1 year) for suspect or confirmed cases of C. auris at the institution. Set up enhanced surveillance for C. auris in the laboratory setting.
Echinocandin drugs are the first-line treatment for most invasive Candida infections, making resistance to this class of antifungal drugs particularly concerning. As of Sept. 15, 2017, at least five patients in the United States had echinocandin-resistant isolates. In one patient, resistance to echinocandin drugs developed while being treated with echinocandins.
Based on these findings, CDC is concerned that echinocandin-resistant C. auris could become more common. Patients with C. auris infection should be closely monitored for treatment failure, as indicated by persistently positive clinical cultures (lasting more than 5 days). Consultation with an infectious disease specialist is highly recommended.
Dr. Tirupathi is medical director, infectious diseases/HIV at Keystone Health, and chair, infection prevention, at Summit Health, both in Chambersburg, Pa. He is clinical assistant professor of medicine at Penn State University, Hershey.
Noninvasive ventilation during exercise benefited a subgroup of COPD patients
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
REPORTING FROM ATS 2018
Key clinical point: Noninvasive ventilation (NIV) during exercise seems feasible and could provide an opportunity to improve endurance training outcomes in selected chronic obstructive pulmonary disease patients.
Major finding: During constant work rate tests patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013).
Study details: A randomized trial of short-term effects of NIV during exercise in 20 hypercapnic patients with very severe COPD.
Disclosures: Ms. Schneeberger reported having no financial disclosures.
Source: Schneeberger T et al. ATS 2018, Abstract A2453.
Effort to phenotype pulmonary hypertension patients under way
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
AT ATS 2018
FDA approves topical anticholinergic for primary axillary hyperhidrosis
The in adults and children aged 9 years and older.
Glycopyrronium, which is formulated in a cloth wipe, will be marketed as Qbrexza and is expected to be available in October, according to the approval announcement June 29, which was made by Dermira, the manufacturer. The instructions for use section in the prescribing information states that patients are advised to use one cloth to apply the medication to both axillae, wiping the cloth across each underarm. Each cloth, intended for single use, is pre-moistened with 2.4% glycopyrronium solution.
Glycopyrronium blocks sweat production “by inhibiting the interaction between acetylcholine and the cholinergic receptors responsible for sweat gland activation,” the company said in a February press release.
The approval was based on the results of two phase 3 clinical studies, ATMOS-1 and ATMOS-2, which were multicenter, randomized, double-blind, vehicle-controlled, 4-week studies in patients 9 years of age or older with primary axillary hyperhidrosis for 6 months or longer. Study subjects had production of at least 50 mg of underarm sweat over 5 minutes, and scores of four or higher on the 11-point Axillary Sweating Daily Diary (ASDD) or the Children’s ASDD (ASDD-C) – an instrument developed by the company in consultation with the FDA – and scores of three or four on the four-grade Hyperhidrosis Disease Severity Scale (HDSS). In total, 463 patients were randomized to receive glycopyrronium and 234 to vehicle. Forty four of these patients were aged 9-16 years, with 25 receiving glycopyrronium and 19 receiving vehicle.
According to the February release, the ASDD/ASDD-C severity scale responder rates were about 60% in the pediatric and adult groups treated with glycopyrronium, compared with 13.0% and 28.8% for children and adults, respectively, in the vehicle group. At week 4, the median absolute change in sweat production was a reduction of 64.2 mg in children and a reduction of 80.6 mg among adults treated with glycopyrronium, compared with reductions of 53.7 mg and 62 mg among those in the vehicle group, respectively.
In the glycopyrronium-treated group, almost 80% of the pediatric patients and 74.3% of the adults experienced at least a 50% reduction in sweat production at week 4, compared with almost 55% and 53%, respectively, in the vehicle group.
Among pediatric patients, the mean decrease from baseline in the Children’s Dermatology Quality of Life Index was 8.1 in glycopyrronium-treated patients, compared with 1.9 in the vehicle group. In adults, scores on the Dermatology Life Quality Index measure were reduced by 8.4 and 4.7 in glycopyrronium- and vehicle-treated adult patients, respectively.
Nearly 57% of adults and 44% of pediatric patients treated with glycopyrronium experienced treatment-emergent adverse events, compared with 34.3% of adults and 10.5% of the pediatric patients in the vehicle group. The majority were related to anticholinergic activity and were mild, and rarely led to drug discontinuation, according to the company.
The press release announcing the approval stated that the most common adverse effects observed after application of glycopyrronium were dry mouth, mydriasis, sore throat, headache, urinary hesitation, blurred vision, dry nose, dry throat, dry eye, dry skin and constipation. Erythema, burning/stinging, and pruritus were the most common skin reactions.
The product is contraindicated in patients with glaucoma, paralytic ileus, and other medical conditions that can be exacerbated by its anticholinergic effects, according to the prescribing information. Patients should be advised that they should wash their hands thoroughly after application, and that it can cause temporary dilation of the pupils and blurred vision if glycopyrronium comes into contact with their eyes.
The in adults and children aged 9 years and older.
Glycopyrronium, which is formulated in a cloth wipe, will be marketed as Qbrexza and is expected to be available in October, according to the approval announcement June 29, which was made by Dermira, the manufacturer. The instructions for use section in the prescribing information states that patients are advised to use one cloth to apply the medication to both axillae, wiping the cloth across each underarm. Each cloth, intended for single use, is pre-moistened with 2.4% glycopyrronium solution.
Glycopyrronium blocks sweat production “by inhibiting the interaction between acetylcholine and the cholinergic receptors responsible for sweat gland activation,” the company said in a February press release.
The approval was based on the results of two phase 3 clinical studies, ATMOS-1 and ATMOS-2, which were multicenter, randomized, double-blind, vehicle-controlled, 4-week studies in patients 9 years of age or older with primary axillary hyperhidrosis for 6 months or longer. Study subjects had production of at least 50 mg of underarm sweat over 5 minutes, and scores of four or higher on the 11-point Axillary Sweating Daily Diary (ASDD) or the Children’s ASDD (ASDD-C) – an instrument developed by the company in consultation with the FDA – and scores of three or four on the four-grade Hyperhidrosis Disease Severity Scale (HDSS). In total, 463 patients were randomized to receive glycopyrronium and 234 to vehicle. Forty four of these patients were aged 9-16 years, with 25 receiving glycopyrronium and 19 receiving vehicle.
According to the February release, the ASDD/ASDD-C severity scale responder rates were about 60% in the pediatric and adult groups treated with glycopyrronium, compared with 13.0% and 28.8% for children and adults, respectively, in the vehicle group. At week 4, the median absolute change in sweat production was a reduction of 64.2 mg in children and a reduction of 80.6 mg among adults treated with glycopyrronium, compared with reductions of 53.7 mg and 62 mg among those in the vehicle group, respectively.
In the glycopyrronium-treated group, almost 80% of the pediatric patients and 74.3% of the adults experienced at least a 50% reduction in sweat production at week 4, compared with almost 55% and 53%, respectively, in the vehicle group.
Among pediatric patients, the mean decrease from baseline in the Children’s Dermatology Quality of Life Index was 8.1 in glycopyrronium-treated patients, compared with 1.9 in the vehicle group. In adults, scores on the Dermatology Life Quality Index measure were reduced by 8.4 and 4.7 in glycopyrronium- and vehicle-treated adult patients, respectively.
Nearly 57% of adults and 44% of pediatric patients treated with glycopyrronium experienced treatment-emergent adverse events, compared with 34.3% of adults and 10.5% of the pediatric patients in the vehicle group. The majority were related to anticholinergic activity and were mild, and rarely led to drug discontinuation, according to the company.
The press release announcing the approval stated that the most common adverse effects observed after application of glycopyrronium were dry mouth, mydriasis, sore throat, headache, urinary hesitation, blurred vision, dry nose, dry throat, dry eye, dry skin and constipation. Erythema, burning/stinging, and pruritus were the most common skin reactions.
The product is contraindicated in patients with glaucoma, paralytic ileus, and other medical conditions that can be exacerbated by its anticholinergic effects, according to the prescribing information. Patients should be advised that they should wash their hands thoroughly after application, and that it can cause temporary dilation of the pupils and blurred vision if glycopyrronium comes into contact with their eyes.
The in adults and children aged 9 years and older.
Glycopyrronium, which is formulated in a cloth wipe, will be marketed as Qbrexza and is expected to be available in October, according to the approval announcement June 29, which was made by Dermira, the manufacturer. The instructions for use section in the prescribing information states that patients are advised to use one cloth to apply the medication to both axillae, wiping the cloth across each underarm. Each cloth, intended for single use, is pre-moistened with 2.4% glycopyrronium solution.
Glycopyrronium blocks sweat production “by inhibiting the interaction between acetylcholine and the cholinergic receptors responsible for sweat gland activation,” the company said in a February press release.
The approval was based on the results of two phase 3 clinical studies, ATMOS-1 and ATMOS-2, which were multicenter, randomized, double-blind, vehicle-controlled, 4-week studies in patients 9 years of age or older with primary axillary hyperhidrosis for 6 months or longer. Study subjects had production of at least 50 mg of underarm sweat over 5 minutes, and scores of four or higher on the 11-point Axillary Sweating Daily Diary (ASDD) or the Children’s ASDD (ASDD-C) – an instrument developed by the company in consultation with the FDA – and scores of three or four on the four-grade Hyperhidrosis Disease Severity Scale (HDSS). In total, 463 patients were randomized to receive glycopyrronium and 234 to vehicle. Forty four of these patients were aged 9-16 years, with 25 receiving glycopyrronium and 19 receiving vehicle.
According to the February release, the ASDD/ASDD-C severity scale responder rates were about 60% in the pediatric and adult groups treated with glycopyrronium, compared with 13.0% and 28.8% for children and adults, respectively, in the vehicle group. At week 4, the median absolute change in sweat production was a reduction of 64.2 mg in children and a reduction of 80.6 mg among adults treated with glycopyrronium, compared with reductions of 53.7 mg and 62 mg among those in the vehicle group, respectively.
In the glycopyrronium-treated group, almost 80% of the pediatric patients and 74.3% of the adults experienced at least a 50% reduction in sweat production at week 4, compared with almost 55% and 53%, respectively, in the vehicle group.
Among pediatric patients, the mean decrease from baseline in the Children’s Dermatology Quality of Life Index was 8.1 in glycopyrronium-treated patients, compared with 1.9 in the vehicle group. In adults, scores on the Dermatology Life Quality Index measure were reduced by 8.4 and 4.7 in glycopyrronium- and vehicle-treated adult patients, respectively.
Nearly 57% of adults and 44% of pediatric patients treated with glycopyrronium experienced treatment-emergent adverse events, compared with 34.3% of adults and 10.5% of the pediatric patients in the vehicle group. The majority were related to anticholinergic activity and were mild, and rarely led to drug discontinuation, according to the company.
The press release announcing the approval stated that the most common adverse effects observed after application of glycopyrronium were dry mouth, mydriasis, sore throat, headache, urinary hesitation, blurred vision, dry nose, dry throat, dry eye, dry skin and constipation. Erythema, burning/stinging, and pruritus were the most common skin reactions.
The product is contraindicated in patients with glaucoma, paralytic ileus, and other medical conditions that can be exacerbated by its anticholinergic effects, according to the prescribing information. Patients should be advised that they should wash their hands thoroughly after application, and that it can cause temporary dilation of the pupils and blurred vision if glycopyrronium comes into contact with their eyes.
Elderly patients with psoriasis can benefit from biologics with low rates of adverse events
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
according to a new retrospective study.
Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.
Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.
As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”
To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.
The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.
The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.
Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.
The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.
The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.
The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.
There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.
Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).
None of the authors had financial disclosures, and the study had no funding source.
SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Key clinical point: Patients aged 65 years and older responded well to biologics and had a low rate of serious adverse events.
Major finding: At 1 year, 65% achieved a PASI 75, 50% achieved a reached PASI 90, and 40% achieved a PASI 100, with a 9.4% rate of serious adverse events.
Study details: The retrospective study comprised 266 patients aged 65 years and older treated with biologics for psoriasis.
Disclosures: None of the authors had financial disclosures, and the study had no funding source.
Source: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018. doi: 10.1111/jdv.15139.
Low risk of complications from sedation-associated GI endoscopies
Background: Most GI endoscopies use sedation to keep patients comfortable during procedures, but sedation puts patients at increased risk of complications. Most of the available studies reporting sedation-related complications are retrospective and dated. There is a lack of prospective studies investigating sedation-related complications and their associated risk factors.
Study design: Prospective study.
Setting: Thirty-nine hospitals in Germany.
Synopsis: Using data collected from 314,190 adult endoscopies in which sedation was used, this study identified that there was only a 0.01% rate of major complications. Major complications for this study included intubation, ICU admission, resuscitation, or death. Propofol was the most commonly used sedative (61.7% of cases) and had the lowest risk of complications (odds ratio, 0.7509; P = .028). The top risk factors for complications were an American Society of Anesthesiologists class greater than 2 (OR, 2.2998; P less than .001), emergent need for the endoscopy (9 of the 13 fatal cases), and longer procedure length (P less than .001).
Bottom line: GI endoscopic procedures with sedation are tolerated well in the general population and have low risk of complications.
Citation: Behrens A et al. Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): Results from the prospective multicentre electronic registry of sedation-associated complications. Gut. 2018 Jan 3. doi: 10.1136/gutjnl-2015-311037.
Dr. Ally is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.
Background: Most GI endoscopies use sedation to keep patients comfortable during procedures, but sedation puts patients at increased risk of complications. Most of the available studies reporting sedation-related complications are retrospective and dated. There is a lack of prospective studies investigating sedation-related complications and their associated risk factors.
Study design: Prospective study.
Setting: Thirty-nine hospitals in Germany.
Synopsis: Using data collected from 314,190 adult endoscopies in which sedation was used, this study identified that there was only a 0.01% rate of major complications. Major complications for this study included intubation, ICU admission, resuscitation, or death. Propofol was the most commonly used sedative (61.7% of cases) and had the lowest risk of complications (odds ratio, 0.7509; P = .028). The top risk factors for complications were an American Society of Anesthesiologists class greater than 2 (OR, 2.2998; P less than .001), emergent need for the endoscopy (9 of the 13 fatal cases), and longer procedure length (P less than .001).
Bottom line: GI endoscopic procedures with sedation are tolerated well in the general population and have low risk of complications.
Citation: Behrens A et al. Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): Results from the prospective multicentre electronic registry of sedation-associated complications. Gut. 2018 Jan 3. doi: 10.1136/gutjnl-2015-311037.
Dr. Ally is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.
Background: Most GI endoscopies use sedation to keep patients comfortable during procedures, but sedation puts patients at increased risk of complications. Most of the available studies reporting sedation-related complications are retrospective and dated. There is a lack of prospective studies investigating sedation-related complications and their associated risk factors.
Study design: Prospective study.
Setting: Thirty-nine hospitals in Germany.
Synopsis: Using data collected from 314,190 adult endoscopies in which sedation was used, this study identified that there was only a 0.01% rate of major complications. Major complications for this study included intubation, ICU admission, resuscitation, or death. Propofol was the most commonly used sedative (61.7% of cases) and had the lowest risk of complications (odds ratio, 0.7509; P = .028). The top risk factors for complications were an American Society of Anesthesiologists class greater than 2 (OR, 2.2998; P less than .001), emergent need for the endoscopy (9 of the 13 fatal cases), and longer procedure length (P less than .001).
Bottom line: GI endoscopic procedures with sedation are tolerated well in the general population and have low risk of complications.
Citation: Behrens A et al. Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): Results from the prospective multicentre electronic registry of sedation-associated complications. Gut. 2018 Jan 3. doi: 10.1136/gutjnl-2015-311037.
Dr. Ally is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.