User login
Sapien M3 mitral valve replacement data reported for first 10 patients
WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.
The docking system “is retrievable up until the point of the final release,” Dr. Webb explained. A knitted polyethylene terephthalate skirt is employed to aid in creating a seal between the leaflets and the dock. Once the docking system is in place, the procedure “then becomes a relatively standard transcatheter transseptal valve-in-valve–type procedure” that is a “fairly easy part of the procedure at centers with transcatheter valve implantation experience.”
The very first case was performed in a 75-year-old woman with severe mitral valve insufficiency. Frail with multiple comorbidities and a left ventricular ejection fraction of 30%, the patient was not a candidate for surgery. Although Dr. Webb acknowledged that the first case “was a learning process,” he reported that the patient was discharged after a 1-night hospital stay with reassuring valve placement and function based on imaging studies.
Data was available from 10 patients from five participating centers in Canada and the United States. The mean age was 74 years, and all were New York Heart Association class III or higher. The mean left ventricular ejection fraction was 37.5%. Although the average Society of Thoracic Surgery risk score was only 4.9%, Dr. Webb noted that this underestimated the vulnerability of a population in which most had compromised renal function. Half of the 10 had severe mitral valve regurgitation prior to valve replacement, and the remainder had moderate to severe regurgitation.
“At the end of 30 days, all had mild or less insufficiency,” Dr. Webb reported. Although one patient did develop significant mitral insufficiency after discharge because of a small tear attributed to probing, it was repaired with a plug. The one technical failure occurred in a patient who required a plug during the course of valve replacement; again, the plug proved effective for preventing significant valve insufficiency.
In this series of patients, one stroke occurred 2 days after the procedure, but there were no deaths in the initial 30-day follow-up, according to Dr. Webb. Although he noted that the procedure time in the first case was 4 hours, the procedure times became shorter with experience and the second-to-last and last cases took 2.5 and 1.3 hours, respectively.
Howard C. Herrmann, MD, director of the interventional cardiology program at the University of Pennsylvania, Philadelphia, and a panelist on the symposium where these data were presented, called the results “exciting.” However, he also noted that “this is the first time that any us have had a look at this device,” so more data will be needed to understand its clinical potential.
Edwards Lifesciences sponsored this study. Dr. Webb reported financial relationships with Abbott Vascular, Edwards Lifesciences, Essential Medical, and Vivitro.
WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.
The docking system “is retrievable up until the point of the final release,” Dr. Webb explained. A knitted polyethylene terephthalate skirt is employed to aid in creating a seal between the leaflets and the dock. Once the docking system is in place, the procedure “then becomes a relatively standard transcatheter transseptal valve-in-valve–type procedure” that is a “fairly easy part of the procedure at centers with transcatheter valve implantation experience.”
The very first case was performed in a 75-year-old woman with severe mitral valve insufficiency. Frail with multiple comorbidities and a left ventricular ejection fraction of 30%, the patient was not a candidate for surgery. Although Dr. Webb acknowledged that the first case “was a learning process,” he reported that the patient was discharged after a 1-night hospital stay with reassuring valve placement and function based on imaging studies.
Data was available from 10 patients from five participating centers in Canada and the United States. The mean age was 74 years, and all were New York Heart Association class III or higher. The mean left ventricular ejection fraction was 37.5%. Although the average Society of Thoracic Surgery risk score was only 4.9%, Dr. Webb noted that this underestimated the vulnerability of a population in which most had compromised renal function. Half of the 10 had severe mitral valve regurgitation prior to valve replacement, and the remainder had moderate to severe regurgitation.
“At the end of 30 days, all had mild or less insufficiency,” Dr. Webb reported. Although one patient did develop significant mitral insufficiency after discharge because of a small tear attributed to probing, it was repaired with a plug. The one technical failure occurred in a patient who required a plug during the course of valve replacement; again, the plug proved effective for preventing significant valve insufficiency.
In this series of patients, one stroke occurred 2 days after the procedure, but there were no deaths in the initial 30-day follow-up, according to Dr. Webb. Although he noted that the procedure time in the first case was 4 hours, the procedure times became shorter with experience and the second-to-last and last cases took 2.5 and 1.3 hours, respectively.
Howard C. Herrmann, MD, director of the interventional cardiology program at the University of Pennsylvania, Philadelphia, and a panelist on the symposium where these data were presented, called the results “exciting.” However, he also noted that “this is the first time that any us have had a look at this device,” so more data will be needed to understand its clinical potential.
Edwards Lifesciences sponsored this study. Dr. Webb reported financial relationships with Abbott Vascular, Edwards Lifesciences, Essential Medical, and Vivitro.
WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.
The docking system “is retrievable up until the point of the final release,” Dr. Webb explained. A knitted polyethylene terephthalate skirt is employed to aid in creating a seal between the leaflets and the dock. Once the docking system is in place, the procedure “then becomes a relatively standard transcatheter transseptal valve-in-valve–type procedure” that is a “fairly easy part of the procedure at centers with transcatheter valve implantation experience.”
The very first case was performed in a 75-year-old woman with severe mitral valve insufficiency. Frail with multiple comorbidities and a left ventricular ejection fraction of 30%, the patient was not a candidate for surgery. Although Dr. Webb acknowledged that the first case “was a learning process,” he reported that the patient was discharged after a 1-night hospital stay with reassuring valve placement and function based on imaging studies.
Data was available from 10 patients from five participating centers in Canada and the United States. The mean age was 74 years, and all were New York Heart Association class III or higher. The mean left ventricular ejection fraction was 37.5%. Although the average Society of Thoracic Surgery risk score was only 4.9%, Dr. Webb noted that this underestimated the vulnerability of a population in which most had compromised renal function. Half of the 10 had severe mitral valve regurgitation prior to valve replacement, and the remainder had moderate to severe regurgitation.
“At the end of 30 days, all had mild or less insufficiency,” Dr. Webb reported. Although one patient did develop significant mitral insufficiency after discharge because of a small tear attributed to probing, it was repaired with a plug. The one technical failure occurred in a patient who required a plug during the course of valve replacement; again, the plug proved effective for preventing significant valve insufficiency.
In this series of patients, one stroke occurred 2 days after the procedure, but there were no deaths in the initial 30-day follow-up, according to Dr. Webb. Although he noted that the procedure time in the first case was 4 hours, the procedure times became shorter with experience and the second-to-last and last cases took 2.5 and 1.3 hours, respectively.
Howard C. Herrmann, MD, director of the interventional cardiology program at the University of Pennsylvania, Philadelphia, and a panelist on the symposium where these data were presented, called the results “exciting.” However, he also noted that “this is the first time that any us have had a look at this device,” so more data will be needed to understand its clinical potential.
Edwards Lifesciences sponsored this study. Dr. Webb reported financial relationships with Abbott Vascular, Edwards Lifesciences, Essential Medical, and Vivitro.
REPORTING FROM CRT 2018
Key clinical point: Initial experience with a transcatheter transseptal mitral valve replacement is encouraging.
Major finding: In the first 10 patients, technical success was achieved in 9.
Study details: A summary of first clinical experience at multiple centers.
Disclosures: Edwards Lifesciences sponsored this study. Dr. Webb reported financial relationships with Abbott Vascular, Edwards Lifesciences, Essential Medical, and Vivitro.
Checkpoint inhibitors well tolerated by NSCLC patients with preexisting autoimmune disease
For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.
Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.
Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.
The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.
Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.
Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.
Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.
“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.
SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.
*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.
For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.
Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.
Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.
The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.
Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.
Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.
Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.
“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.
SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.
*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.
For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.
Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.
Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.
The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.
Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.
Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.
Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.
“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.
SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.
*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Eleven percent of patients with autoimmune disease experienced grade 3 or 4 immune-related adverse events, compared with 7%-15% of patients without autoimmune disease.
Study details: A retrospective study of 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers.
Disclosures: The Kaplan Research Fund and Jeni Fund, Memorial Sloan Kettering Cancer Center, the American Cancer Society, and the University of Texas MD Anderson Cancer Center sponsored the study. The researchers reported receiving financial support from Merck, Novartis, Genentech, and other companies.
Source: Leonardi GC et al. J Clin Oncol. 2018 May 20. doi: 10.1200/JCO.2017.77.0305.
IMDC model mirrors mRCC clinical outcomes
In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.
By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.
“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.
They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.
They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.
In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.
They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.
They found that for sunitinib-treated patients in the IMDC favorable-risk group, median PFS was 14.1 months, compared with 10.7 months for those in the intermediate-risk group, 2,4 months in the poor-risk group, and 10.6 months for the combined intermediate and poor-risk groups.
The respective objective response rates were 53%, 33.7%, 11.8%, and 30.5%.
Median overall survival for favorable-risk patients was not reached, with more than 50% of patients alive at the time of data cutoff. The respective median overall survival for the intermediate-, poor-, and intermediate-plus-poor–risk groups were 23, 5.1, and 20.3 months.
“Results of this study suggest there may be significant prognostic differences between the intermediate-1 and intermediate-2 IMDC risk groups and that this should be considered when counseling patients identified to be in one of these groups,” the investigators wrote.
Medical writing for the study was supported by Pfizer. Dr. Rini and his coauthors disclosed research funding and/or consulting fees from Pfizer and other companies. Four of the coauthors are Pfizer employees and stockholders.
SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.
In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.
By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.
“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.
They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.
They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.
In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.
They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.
They found that for sunitinib-treated patients in the IMDC favorable-risk group, median PFS was 14.1 months, compared with 10.7 months for those in the intermediate-risk group, 2,4 months in the poor-risk group, and 10.6 months for the combined intermediate and poor-risk groups.
The respective objective response rates were 53%, 33.7%, 11.8%, and 30.5%.
Median overall survival for favorable-risk patients was not reached, with more than 50% of patients alive at the time of data cutoff. The respective median overall survival for the intermediate-, poor-, and intermediate-plus-poor–risk groups were 23, 5.1, and 20.3 months.
“Results of this study suggest there may be significant prognostic differences between the intermediate-1 and intermediate-2 IMDC risk groups and that this should be considered when counseling patients identified to be in one of these groups,” the investigators wrote.
Medical writing for the study was supported by Pfizer. Dr. Rini and his coauthors disclosed research funding and/or consulting fees from Pfizer and other companies. Four of the coauthors are Pfizer employees and stockholders.
SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.
In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.
By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.
“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.
They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.
They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.
In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.
They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.
They found that for sunitinib-treated patients in the IMDC favorable-risk group, median PFS was 14.1 months, compared with 10.7 months for those in the intermediate-risk group, 2,4 months in the poor-risk group, and 10.6 months for the combined intermediate and poor-risk groups.
The respective objective response rates were 53%, 33.7%, 11.8%, and 30.5%.
Median overall survival for favorable-risk patients was not reached, with more than 50% of patients alive at the time of data cutoff. The respective median overall survival for the intermediate-, poor-, and intermediate-plus-poor–risk groups were 23, 5.1, and 20.3 months.
“Results of this study suggest there may be significant prognostic differences between the intermediate-1 and intermediate-2 IMDC risk groups and that this should be considered when counseling patients identified to be in one of these groups,” the investigators wrote.
Medical writing for the study was supported by Pfizer. Dr. Rini and his coauthors disclosed research funding and/or consulting fees from Pfizer and other companies. Four of the coauthors are Pfizer employees and stockholders.
SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.
FROM CLINICAL GENITOURINARY CANCER
Key clinical point: The IMDC model is prognostic for responses and survival in patients with mRCC treated with sunitinib.
Major finding: Median progression-free survival for favorable, intermediate, and poor-risk patients was 14.1, 10.7, and 2.4 months, respectively.
Study details: Retrospective analysis of 375 sunitinib-treated patients in a randomized clinical trial.
Disclosures: Medical writing for the study was supported by Pfizer. Dr. Rini and his coauthors disclosed research funding and/or consulting fees from Pfizer and other companies. Four of the coauthors are Pfizer employees and stockholders.
Source: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.
For in-stent restenosis, everolimus-eluting stents topped drug-eluting balloons
For patients with coronary artery restenosis at the site of a drug-eluting stent, placing an everolimus-eluting stent was associated with a 57% lower risk of target lesion revascularization, compared with placing a drug-eluting balloon.
At 3-year follow-up in the randomized, multicenter RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial, 7.1% of patients required target lesion revascularization after EES versus 15.6% of patients after DEB (P = .015), reported Fernando Alfonso, MD, of Hospital Universitario de La Princesa, Madrid, and his associates. Consequently, the combined rate of cardiac death, myocardial infarction, and target lesion revascularization was 12.3% with EES versus 20.1% with DEB (hazard ratio, 0.57; 95% confidence interval, 0.34-0.96; P = .04). The findings were reported in JACC: Cardiovascular Interventions.
About 5%-10% of patients who receive a drug-eluting stent (DES) develop in-stent restenosis (ISR). When this happens, robust data support placing a DEB or next-generation DES, such as an EES, instead of a conventional (plain) balloon, the investigators noted. To directly compare EES versus DEB, they randomly assigned 309 patients with at least 50% lumen diameter stenosis at the DES site or involving its 5-mm edge to receive either DEB (SeQuent Please, B. Braun) with a 1.1:1 balloon-to-artery ratio (mean 18 atm [pressure]), or EES (Xience Prime, Abbott Vascular) with the same final ratio but significantly greater deployment pressure (mean 20 arm; P = .001). All patients had angina or objective evidence of ischemia without stent thrombosis, and the trial arms otherwise resembled each other clinically and demographically.
Angiography documented 100% immediate procedural success in both groups. At 1 year, rates of target lesion revascularization were 4.5% with EES and 13% with DEB, a significant difference (HR, 0.33; 95% CI, 0.14-0.79). Similarly, rates of target vessel revascularization were 8.4% and 16.2%, respectively (HR, 0.49; 95% CI, 0.25-0.97), at year 1 and 11% and 20.8%, respectively, at year 3 (HR, 0.50; 95% CI, 0.28-0.90).
Throughout the study, including at 3 years, the groups had similar rates of cardiac death (3.9% for EES vs. 3.2% for DEB), MI (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%). “Results of other composite clinical outcomes [also] were very similar,” the researchers wrote. While “both DEB and EES provide favorable long-term clinical outcomes,” patients “receiving EES benefit[ed] from a better long-term clinical outcome, mainly driven by a reduced need of target lesion and target vessel revascularization.”
Funders of the study included B. Braun and Abbott Vascular. The investigators reported having no conflicts of interest.
SOURCE: Alfonso F et al. JACC Cardiovasc Interv. 2018;11:981-91.
Three-year outcomes favored everolimus-eluting stents (EES) over drug-eluting balloons (DEBs) for treating in-stent restenosis, but this “should not be a reason to bid farewell to DEBs,” wrote Hyo-Soo Kim, MD, PhD, and Tae-Min Rhee, MD, in an editorial accompanying the study.
Both EES and DEB have excellent long-term safety, so a “simple rivalry between the [two] arms is no longer meaningful,” they wrote in JACC: Cardiovascular Interventions. “Instead, it is time to find ways to improve the efficacy of DEBs.”
The efficacy of DEB depends on the amount of antiproliferative drug delivered to the target lesion, which isn’t the case for EES, the experts noted. In past studies, independent predictors of long-term DEBs success included less than 20% residual stenosis, balloon-to-stent ratio exceeding 0.91, and inflation time above 60 seconds, they added. When all three of these criteria were met, DEBs performed as well as new-generation drug-eluting stents.
Thus, DEBs retains a treatment niche, “particularly for in-stent restenosis lesions already covered with one or more metal layers.”
Dr. Kim and Dr. Rhee are with Seoul (South Korea) National University Hospital. They reported having no conflicts of interest. These comments are from their editorial (JACC Cardiovasc Interv. 2018;11:992-4).
Three-year outcomes favored everolimus-eluting stents (EES) over drug-eluting balloons (DEBs) for treating in-stent restenosis, but this “should not be a reason to bid farewell to DEBs,” wrote Hyo-Soo Kim, MD, PhD, and Tae-Min Rhee, MD, in an editorial accompanying the study.
Both EES and DEB have excellent long-term safety, so a “simple rivalry between the [two] arms is no longer meaningful,” they wrote in JACC: Cardiovascular Interventions. “Instead, it is time to find ways to improve the efficacy of DEBs.”
The efficacy of DEB depends on the amount of antiproliferative drug delivered to the target lesion, which isn’t the case for EES, the experts noted. In past studies, independent predictors of long-term DEBs success included less than 20% residual stenosis, balloon-to-stent ratio exceeding 0.91, and inflation time above 60 seconds, they added. When all three of these criteria were met, DEBs performed as well as new-generation drug-eluting stents.
Thus, DEBs retains a treatment niche, “particularly for in-stent restenosis lesions already covered with one or more metal layers.”
Dr. Kim and Dr. Rhee are with Seoul (South Korea) National University Hospital. They reported having no conflicts of interest. These comments are from their editorial (JACC Cardiovasc Interv. 2018;11:992-4).
Three-year outcomes favored everolimus-eluting stents (EES) over drug-eluting balloons (DEBs) for treating in-stent restenosis, but this “should not be a reason to bid farewell to DEBs,” wrote Hyo-Soo Kim, MD, PhD, and Tae-Min Rhee, MD, in an editorial accompanying the study.
Both EES and DEB have excellent long-term safety, so a “simple rivalry between the [two] arms is no longer meaningful,” they wrote in JACC: Cardiovascular Interventions. “Instead, it is time to find ways to improve the efficacy of DEBs.”
The efficacy of DEB depends on the amount of antiproliferative drug delivered to the target lesion, which isn’t the case for EES, the experts noted. In past studies, independent predictors of long-term DEBs success included less than 20% residual stenosis, balloon-to-stent ratio exceeding 0.91, and inflation time above 60 seconds, they added. When all three of these criteria were met, DEBs performed as well as new-generation drug-eluting stents.
Thus, DEBs retains a treatment niche, “particularly for in-stent restenosis lesions already covered with one or more metal layers.”
Dr. Kim and Dr. Rhee are with Seoul (South Korea) National University Hospital. They reported having no conflicts of interest. These comments are from their editorial (JACC Cardiovasc Interv. 2018;11:992-4).
For patients with coronary artery restenosis at the site of a drug-eluting stent, placing an everolimus-eluting stent was associated with a 57% lower risk of target lesion revascularization, compared with placing a drug-eluting balloon.
At 3-year follow-up in the randomized, multicenter RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial, 7.1% of patients required target lesion revascularization after EES versus 15.6% of patients after DEB (P = .015), reported Fernando Alfonso, MD, of Hospital Universitario de La Princesa, Madrid, and his associates. Consequently, the combined rate of cardiac death, myocardial infarction, and target lesion revascularization was 12.3% with EES versus 20.1% with DEB (hazard ratio, 0.57; 95% confidence interval, 0.34-0.96; P = .04). The findings were reported in JACC: Cardiovascular Interventions.
About 5%-10% of patients who receive a drug-eluting stent (DES) develop in-stent restenosis (ISR). When this happens, robust data support placing a DEB or next-generation DES, such as an EES, instead of a conventional (plain) balloon, the investigators noted. To directly compare EES versus DEB, they randomly assigned 309 patients with at least 50% lumen diameter stenosis at the DES site or involving its 5-mm edge to receive either DEB (SeQuent Please, B. Braun) with a 1.1:1 balloon-to-artery ratio (mean 18 atm [pressure]), or EES (Xience Prime, Abbott Vascular) with the same final ratio but significantly greater deployment pressure (mean 20 arm; P = .001). All patients had angina or objective evidence of ischemia without stent thrombosis, and the trial arms otherwise resembled each other clinically and demographically.
Angiography documented 100% immediate procedural success in both groups. At 1 year, rates of target lesion revascularization were 4.5% with EES and 13% with DEB, a significant difference (HR, 0.33; 95% CI, 0.14-0.79). Similarly, rates of target vessel revascularization were 8.4% and 16.2%, respectively (HR, 0.49; 95% CI, 0.25-0.97), at year 1 and 11% and 20.8%, respectively, at year 3 (HR, 0.50; 95% CI, 0.28-0.90).
Throughout the study, including at 3 years, the groups had similar rates of cardiac death (3.9% for EES vs. 3.2% for DEB), MI (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%). “Results of other composite clinical outcomes [also] were very similar,” the researchers wrote. While “both DEB and EES provide favorable long-term clinical outcomes,” patients “receiving EES benefit[ed] from a better long-term clinical outcome, mainly driven by a reduced need of target lesion and target vessel revascularization.”
Funders of the study included B. Braun and Abbott Vascular. The investigators reported having no conflicts of interest.
SOURCE: Alfonso F et al. JACC Cardiovasc Interv. 2018;11:981-91.
For patients with coronary artery restenosis at the site of a drug-eluting stent, placing an everolimus-eluting stent was associated with a 57% lower risk of target lesion revascularization, compared with placing a drug-eluting balloon.
At 3-year follow-up in the randomized, multicenter RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial, 7.1% of patients required target lesion revascularization after EES versus 15.6% of patients after DEB (P = .015), reported Fernando Alfonso, MD, of Hospital Universitario de La Princesa, Madrid, and his associates. Consequently, the combined rate of cardiac death, myocardial infarction, and target lesion revascularization was 12.3% with EES versus 20.1% with DEB (hazard ratio, 0.57; 95% confidence interval, 0.34-0.96; P = .04). The findings were reported in JACC: Cardiovascular Interventions.
About 5%-10% of patients who receive a drug-eluting stent (DES) develop in-stent restenosis (ISR). When this happens, robust data support placing a DEB or next-generation DES, such as an EES, instead of a conventional (plain) balloon, the investigators noted. To directly compare EES versus DEB, they randomly assigned 309 patients with at least 50% lumen diameter stenosis at the DES site or involving its 5-mm edge to receive either DEB (SeQuent Please, B. Braun) with a 1.1:1 balloon-to-artery ratio (mean 18 atm [pressure]), or EES (Xience Prime, Abbott Vascular) with the same final ratio but significantly greater deployment pressure (mean 20 arm; P = .001). All patients had angina or objective evidence of ischemia without stent thrombosis, and the trial arms otherwise resembled each other clinically and demographically.
Angiography documented 100% immediate procedural success in both groups. At 1 year, rates of target lesion revascularization were 4.5% with EES and 13% with DEB, a significant difference (HR, 0.33; 95% CI, 0.14-0.79). Similarly, rates of target vessel revascularization were 8.4% and 16.2%, respectively (HR, 0.49; 95% CI, 0.25-0.97), at year 1 and 11% and 20.8%, respectively, at year 3 (HR, 0.50; 95% CI, 0.28-0.90).
Throughout the study, including at 3 years, the groups had similar rates of cardiac death (3.9% for EES vs. 3.2% for DEB), MI (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%). “Results of other composite clinical outcomes [also] were very similar,” the researchers wrote. While “both DEB and EES provide favorable long-term clinical outcomes,” patients “receiving EES benefit[ed] from a better long-term clinical outcome, mainly driven by a reduced need of target lesion and target vessel revascularization.”
Funders of the study included B. Braun and Abbott Vascular. The investigators reported having no conflicts of interest.
SOURCE: Alfonso F et al. JACC Cardiovasc Interv. 2018;11:981-91.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
Key clinical point: Everolimus-eluting stents outperformed drug-eluting balloons for patients with restenosis of coronary arteries following initial drug-eluting stent placement.
Major finding: Three-year rates of target lesion revascularization were 7.1% with EES and 15.6% with DEB (P = .015). Consequently, the combined rate of cardiac death, myocardial infarction, and target lesion revascularization was significantly lower with EES (12.3% vs. 20.1% with DEB; P = .04).
Study details: Randomized multicenter trial of 309 patients with blinded outcomes assessment (RIBS IV).
Disclosures: Funders included B. Braun Surgical and Abbott Vascular. The investigators reported having no conflicts of interest.
Source: Alfonso F et al. JACC Cardiovasc Interv. 2018;11:981-91.
CARPREG II fine-tunes assessment of cardiac complication risk in pregnancy
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: A newly developed risk index enhances the ability to predict maternal cardiac complications by combining general, lesion-specific, and delivery-of-care variables.
Major finding: Investigators developed the CARPREG II risk index based on 10 predictors of maternal cardiac complications (5 general, 4 lesion-specific, and 1 related to delivery of care).
Study details: The CARPREG II Study, which included more than 2,000 prospectively enrolled consecutive pregnant women with heart disease seen at one of two large Canadian obstetric centers.
Disclosures: Authors reported that they had no relationships to disclose relevant to the contents of their report on the study.
Source: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
Uvulopalatopharyngoplasty may reduce cardiac risk in sleep apnea
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
Surgical remodeling of the tissues of the throat using uvulopalatopharyngoplasty (UPPP) could significantly reduce the cardiac complications of obstructive sleep apnea (OSA), according to a study published in Sleep Medicine.
Researchers examined the incidence of newly diagnosed myocardial infarction, congestive heart failure, and atrial fibrillation in 192,316 patients with a new diagnosis of obstructive sleep apnea – 22,213 of whom had undergone UPPP – and 961,590 controls.
The individuals who had had UPPP had a significantly lower incidence of all three cardiovascular events, compared with those who had not undergone the procedure. The hazard ratios for myocardial infarction, congestive heart failure, and atrial fibrillation among individuals with OSA who had uvulopalatopharyngoplasty, compared with controls, were 1.002, 0.757 and 1.117, respectively. By comparison, those hazard ratios in patients with OSA who had not had UPPP, compared with controls, were 1.070, 1.165, and 1.39 for myocardial infarction, congestive heart failure, and atrial fibrillation respectively.
These figures were after accounting for confounding factors, such as age, sex, diabetes, hypertension, and dyslipidemia.
The authors wrote that the most distinctive finding of their study was that uvulopalatopharyngoplasty lowered the incidence of congestive heart failure and atrial fibrillation in patients with obstructive sleep apnea to the point that they had the same level of risk as individuals without obstructive sleep apnea.
“Prior studies have evaluated the success of UPPP based on reductions of AHI [apnea-hypopnea index], with the average success rate for the surgery being low for most patients,” wrote Heung-Man Lee, MD, PhD, then from the Guro Hospital at Korea University, Seoul, and his coauthors.
“However, the current study suggests that the effects of UPPP, regardless of the effects on AHI, can significantly reduce cardiac morbidity in patients with OSA.”
Patients without diabetes showed more benefit from UPPP in reducing the incidence of congestive heart failure, compared with those with diabetes. However, those with diabetes showed greater reductions in the risk of atrial fibrillation, compared with those without diabetes.
Similarly, the incidence of atrial fibrillation was reduced after uvulopalatopharyngoplasty but only in patients with hypertension or dyslipidemia and not in those with normal blood pressure or lipid levels.
“These differences in outcomes after UPPP are probably due to the different etiologies of cardiovascular disease,” the authors wrote. “OSA increases free fatty acid in the blood because intermittent hypoxia associated with OSA induces adipose tissue lipolysis.”
One limitation of the study was the absence of polysomnography information. The researchers relied on diagnostic codes for confirmation of OSA. They also did not have information on other sleep apnea therapies, such as CPAP or a mandibular advancing device, which may have been used in the patients who did not undergo uvulopalatopharyngoplasty.
The study was supported by the Korean Society of Otorhinolaryngology Head and Neck Surgery. No conflicts of interest were declared.
SOURCE: Lee HM et al. Sleep Med. 2018 May;45:11-16.
FROM SLEEP MEDICINE
Key clinical point: Uvulopalatopharyngoplasty might avert cardiac complications caused by obstructive sleep apnea.
Major finding: Compared with controls, the hazard ratios for MI, congestive heart failure, and atrial fibrillation 1.002, 0.757, and 1.117, respectively, among individuals with OSA who had had UPPP and 1.070, 1.165, and 1.39 among those who had not had UPPP.
Study details: Study of 192,316 patients with obstructive sleep apnea and 961,590 controls.
Disclosures: The study was supported by the Korean Society of Otorhinolaryngology–Head and Neck Surgery. No conflicts of interest were declared.
Source: Lee HM et al. Sleep Med. 2018 May;45:11-16.
8-Isoprostane levels predict OSA in children
The oxidative stress biomarker 8-isoprostane (8-IsoP) predicted obstructive sleep apnea (OSA) and disease severity in children better than the fractional concentration of exhaled nitric oxide (FENO), according to results published in Sleep Medicine.
In an analysis of 46 patients with sleep-disordered breathing and 20 controls, 8-IsoP values were also correlated with apnea hypopnea index (AHI) (r, 0.40; P = .003) and oxygen saturation, also known as SaO2, (r, –0.50; P = .001), reported Dr. Mario Berreto of the Pediatric Unit at Sant’Andrea Hospital in Rome and his coauthors.
The investigators studied 66 children aged 4.5-15.1 years, of whom 46 had sleep-disordered breathing (SDB) and were enrolled in the hospital’s Pediatric Sleep Center. The 20 healthy controls had no history of sleep problems, including snoring, apneas, and restless sleep. Exclusion criteria included acute respiratory infections in the 4 weeks preceding the study, chronic respiratory comorbidities, and therapy with corticosteroids or other anti-inflammatory drugs for at least 3 weeks.
Patients with SDB had a medical examination followed by overnight standard polysomnography (PSG), and EBC 8-IsoP and FENO measurements were collected the next morning upon waking. The SDB group also had spirometry and skin prick testing for common allergens. The children in the control group had the same tests and measurements done, except for PSG, Dr. Berreto and his colleagues wrote.
Central, obstructive, and mixed apnea events were counted according to American Academy of Sleep Medicine (AASM) criteria. AHI was defined as the average number of apnea and hypopnea events per hour of sleep. OSA was diagnosed with an AHI of one episode per hour and confirmed by the presence of SDB symptoms with AHI of one episode per hour.
Children with snoring and an AHI of less than one episode per hour were diagnosed with primary snoring (PS). Patients with an AHI greater than one episode per hour and less than five episodes per hour were diagnosed with mild OSA. Children with an AHI of greater than five episodes per hour were diagnosed with moderate to severe OSA, the authors said.
While 8-IsoP concentrations correlated with OSA severity for AHI and SaO2, FENO did not, Dr. Berreto and colleagues reported.
The difference in 8-IsoP concentrations for children with SDB and controls (mean, 39.6; P = .006) was increased when adjusted using multiple linear regression (mean, 43.2; P = .007), and the difference was even more pronounced when adjusted for all potential confounding variables (mean, 53.1; P = .008). The difference in FENO levels between SDB patients and controls was not statistically significant (mean, 1.67; P = .358) and did not change significantly when adjusted for confounding variables.
High area under the curve values were observed for 8-IsoP as a predictor of OSA (.839; 95% confidence interval, .744-.933, P = .000). The sensitivity and specificity of cutoff values of 8-IsoP concentrations above the 50th percentile were 76.5% and 78.1%, respectively.
“[It] seems that biomarkers of oxidative stress reflect OSA severity in children more closely than biomarkers of atopic-eosinophilic airway inflammation,” the authors concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Barreto M et al. Sleep Medicine. 2018. doi: 10.1016/j.sleep.2018.01.011.
The oxidative stress biomarker 8-isoprostane (8-IsoP) predicted obstructive sleep apnea (OSA) and disease severity in children better than the fractional concentration of exhaled nitric oxide (FENO), according to results published in Sleep Medicine.
In an analysis of 46 patients with sleep-disordered breathing and 20 controls, 8-IsoP values were also correlated with apnea hypopnea index (AHI) (r, 0.40; P = .003) and oxygen saturation, also known as SaO2, (r, –0.50; P = .001), reported Dr. Mario Berreto of the Pediatric Unit at Sant’Andrea Hospital in Rome and his coauthors.
The investigators studied 66 children aged 4.5-15.1 years, of whom 46 had sleep-disordered breathing (SDB) and were enrolled in the hospital’s Pediatric Sleep Center. The 20 healthy controls had no history of sleep problems, including snoring, apneas, and restless sleep. Exclusion criteria included acute respiratory infections in the 4 weeks preceding the study, chronic respiratory comorbidities, and therapy with corticosteroids or other anti-inflammatory drugs for at least 3 weeks.
Patients with SDB had a medical examination followed by overnight standard polysomnography (PSG), and EBC 8-IsoP and FENO measurements were collected the next morning upon waking. The SDB group also had spirometry and skin prick testing for common allergens. The children in the control group had the same tests and measurements done, except for PSG, Dr. Berreto and his colleagues wrote.
Central, obstructive, and mixed apnea events were counted according to American Academy of Sleep Medicine (AASM) criteria. AHI was defined as the average number of apnea and hypopnea events per hour of sleep. OSA was diagnosed with an AHI of one episode per hour and confirmed by the presence of SDB symptoms with AHI of one episode per hour.
Children with snoring and an AHI of less than one episode per hour were diagnosed with primary snoring (PS). Patients with an AHI greater than one episode per hour and less than five episodes per hour were diagnosed with mild OSA. Children with an AHI of greater than five episodes per hour were diagnosed with moderate to severe OSA, the authors said.
While 8-IsoP concentrations correlated with OSA severity for AHI and SaO2, FENO did not, Dr. Berreto and colleagues reported.
The difference in 8-IsoP concentrations for children with SDB and controls (mean, 39.6; P = .006) was increased when adjusted using multiple linear regression (mean, 43.2; P = .007), and the difference was even more pronounced when adjusted for all potential confounding variables (mean, 53.1; P = .008). The difference in FENO levels between SDB patients and controls was not statistically significant (mean, 1.67; P = .358) and did not change significantly when adjusted for confounding variables.
High area under the curve values were observed for 8-IsoP as a predictor of OSA (.839; 95% confidence interval, .744-.933, P = .000). The sensitivity and specificity of cutoff values of 8-IsoP concentrations above the 50th percentile were 76.5% and 78.1%, respectively.
“[It] seems that biomarkers of oxidative stress reflect OSA severity in children more closely than biomarkers of atopic-eosinophilic airway inflammation,” the authors concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Barreto M et al. Sleep Medicine. 2018. doi: 10.1016/j.sleep.2018.01.011.
The oxidative stress biomarker 8-isoprostane (8-IsoP) predicted obstructive sleep apnea (OSA) and disease severity in children better than the fractional concentration of exhaled nitric oxide (FENO), according to results published in Sleep Medicine.
In an analysis of 46 patients with sleep-disordered breathing and 20 controls, 8-IsoP values were also correlated with apnea hypopnea index (AHI) (r, 0.40; P = .003) and oxygen saturation, also known as SaO2, (r, –0.50; P = .001), reported Dr. Mario Berreto of the Pediatric Unit at Sant’Andrea Hospital in Rome and his coauthors.
The investigators studied 66 children aged 4.5-15.1 years, of whom 46 had sleep-disordered breathing (SDB) and were enrolled in the hospital’s Pediatric Sleep Center. The 20 healthy controls had no history of sleep problems, including snoring, apneas, and restless sleep. Exclusion criteria included acute respiratory infections in the 4 weeks preceding the study, chronic respiratory comorbidities, and therapy with corticosteroids or other anti-inflammatory drugs for at least 3 weeks.
Patients with SDB had a medical examination followed by overnight standard polysomnography (PSG), and EBC 8-IsoP and FENO measurements were collected the next morning upon waking. The SDB group also had spirometry and skin prick testing for common allergens. The children in the control group had the same tests and measurements done, except for PSG, Dr. Berreto and his colleagues wrote.
Central, obstructive, and mixed apnea events were counted according to American Academy of Sleep Medicine (AASM) criteria. AHI was defined as the average number of apnea and hypopnea events per hour of sleep. OSA was diagnosed with an AHI of one episode per hour and confirmed by the presence of SDB symptoms with AHI of one episode per hour.
Children with snoring and an AHI of less than one episode per hour were diagnosed with primary snoring (PS). Patients with an AHI greater than one episode per hour and less than five episodes per hour were diagnosed with mild OSA. Children with an AHI of greater than five episodes per hour were diagnosed with moderate to severe OSA, the authors said.
While 8-IsoP concentrations correlated with OSA severity for AHI and SaO2, FENO did not, Dr. Berreto and colleagues reported.
The difference in 8-IsoP concentrations for children with SDB and controls (mean, 39.6; P = .006) was increased when adjusted using multiple linear regression (mean, 43.2; P = .007), and the difference was even more pronounced when adjusted for all potential confounding variables (mean, 53.1; P = .008). The difference in FENO levels between SDB patients and controls was not statistically significant (mean, 1.67; P = .358) and did not change significantly when adjusted for confounding variables.
High area under the curve values were observed for 8-IsoP as a predictor of OSA (.839; 95% confidence interval, .744-.933, P = .000). The sensitivity and specificity of cutoff values of 8-IsoP concentrations above the 50th percentile were 76.5% and 78.1%, respectively.
“[It] seems that biomarkers of oxidative stress reflect OSA severity in children more closely than biomarkers of atopic-eosinophilic airway inflammation,” the authors concluded.
No disclosures or conflicts of interest were reported.
SOURCE: Barreto M et al. Sleep Medicine. 2018. doi: 10.1016/j.sleep.2018.01.011.
FROM SLEEP MEDICINE
Key clinical point: The biomarker 8-isoprostane predicted OSA and correlated with disease severity in children.
Major finding: Children with OSA had higher levels of 8-IsoP than patients with primary snoring (PS) and controls; 8-IsoP values were also correlated with apnea hypopnea index (r, 0.40; P = .003).
Study details: A single-center, cross-sectional observational study of 46 children with sleep-disordered breathing and 20 healthy controls.
Disclosures: No disclosures or conflicts of interest were reported.
Source: Barreto M et al. Sleep Medicine. 2018. doi: https://doi.org/10.1016/j.sleep.2018.01.011.
Cemiplimab impresses in advanced CSCC
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
REPORTING FROM THE ACMS ANNUAL MEETING
Key clinical point:
Major finding: Disease control was achieved in 11 of 16 patients (69%).
Study details: The open-label, phase 1 study included seven patients with distant metastatic cutaneous squamous cell carcinoma and nine with locally and/or regionally advanced disease.
Disclosures: The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. Dr. Migden reported receiving honoraria from Regeneron and Sanofi as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
New device could noninvasively detect osteoarthritis using sound and motion
LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.
Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.
“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.
The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.
“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”
To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.
The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.
For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.
Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.
A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.
“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.
These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.
“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.
Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”
Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”
Mr. Tiulpin did not have any conflicts of interest to disclose.
SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.
LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.
Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.
“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.
The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.
“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”
To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.
The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.
For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.
Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.
A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.
“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.
These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.
“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.
Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”
Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”
Mr. Tiulpin did not have any conflicts of interest to disclose.
SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.
LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.
Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.
“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.
The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.
“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”
To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.
The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.
For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.
Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.
A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.
“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.
These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.
“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.
Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”
Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”
Mr. Tiulpin did not have any conflicts of interest to disclose.
SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.
REPORTING FROM OARSI 2018
Key clinical point: A prototype device showed a promising application as a noninvasive method to detect osteoarthritis.
Major finding: In a model that combined it with BMI and age, the device had an area under the curve of 84%, which suggested that this device might be able to improve OA detection.
Study details: Single-center study of 66 women aged 44-67 years old; 51.5% had radiographically confirmed OA of Kellgren-Lawrence grade 2 or higher.
Disclosures: Mr. Tiulpin did not have any conflicts of interest to disclose.
Source: Tiulpin A et al. Osteoarthritis Cartilage. 2018;26(1):S40–S41.
FDA Updates
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.