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U.S. death rates from chronic liver disease continue to rise
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
AT THE LIVER MEETING 2018
Key clinical point: Nonalcoholic steatohepatitis is very common in the U.S. population.
Major finding: Between 2007 and 2016, the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population to 24.9/100,000 population.
Study details: An analysis of 838,809 chronic liver disease–related deaths from 2007 to 2016.
Disclosures: Dr. Younossi disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, Bristol-Myers Squibb, AbbVie, Viking, Term Quest Diagnostics, Echosens, and Shionogi. He has also received grant/research support from Gilead, Intercept, and Bristol-Myers Squibb.
Source: Hepatol. 2018;68[S1], Abstract 763.
Biomarkers and concussions
A novel theory explains the variable efficacy of SSRIs, single-dose zoliflodacin is successful for uncomplicated urogenital gonorrhea, and drinking regular, caffeinated coffee is linked with a decreased risk of rosacea.
Amazon Alexa
Apple Podcasts
Spotify
A novel theory explains the variable efficacy of SSRIs, single-dose zoliflodacin is successful for uncomplicated urogenital gonorrhea, and drinking regular, caffeinated coffee is linked with a decreased risk of rosacea.
Amazon Alexa
Apple Podcasts
Spotify
A novel theory explains the variable efficacy of SSRIs, single-dose zoliflodacin is successful for uncomplicated urogenital gonorrhea, and drinking regular, caffeinated coffee is linked with a decreased risk of rosacea.
Amazon Alexa
Apple Podcasts
Spotify
‘Encouraging’ phase 2 results in rel/ref AML
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.
CAR T therapy for MM receives RMAT designation
P-BCMA-101, an autologous chimeric antigen receptor (CAR) T-cell therapy being developed to treat patients with relapsed/refractory multiple myeloma (MM), has received regenerative medicine advanced therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA).
RMAT designation is intended to expedite the development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
For a therapy to receive RMAT designation, preliminary evidence must indicate the therapy has the potential to address unmet medical needs for the disease or condition.
RMAT designation provides all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
About P-BCMA-101
To create P-BCMA-101, patients’ T cells are modified using a non-viral DNA modification system known as piggyBac™. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 trial (NCT03288493) of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.
The presentation included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells—51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near complete response.
Additional results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1012).
The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.
P-BCMA-101, an autologous chimeric antigen receptor (CAR) T-cell therapy being developed to treat patients with relapsed/refractory multiple myeloma (MM), has received regenerative medicine advanced therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA).
RMAT designation is intended to expedite the development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
For a therapy to receive RMAT designation, preliminary evidence must indicate the therapy has the potential to address unmet medical needs for the disease or condition.
RMAT designation provides all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
About P-BCMA-101
To create P-BCMA-101, patients’ T cells are modified using a non-viral DNA modification system known as piggyBac™. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 trial (NCT03288493) of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.
The presentation included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells—51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near complete response.
Additional results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1012).
The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.
P-BCMA-101, an autologous chimeric antigen receptor (CAR) T-cell therapy being developed to treat patients with relapsed/refractory multiple myeloma (MM), has received regenerative medicine advanced therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA).
RMAT designation is intended to expedite the development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
For a therapy to receive RMAT designation, preliminary evidence must indicate the therapy has the potential to address unmet medical needs for the disease or condition.
RMAT designation provides all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
About P-BCMA-101
To create P-BCMA-101, patients’ T cells are modified using a non-viral DNA modification system known as piggyBac™. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 trial (NCT03288493) of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.
The presentation included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells—51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near complete response.
Additional results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1012).
The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.
Vaccine inhibits thrombus formation in mice
Investigators designed an antiplatelet vaccine they say could be a novel therapy to prevent recurrent ischemic stroke.
The vaccine inhibits S100A9 (S100 calcium-binding protein A9)/CD36 (cluster of differentiation 36) signaling in platelets, which is a key signal in arterial thrombosis but not hemostasis.
Mice immunized with the vaccine experienced an antithrombotic effect that lasted 84 days.
The vaccine inhibited thrombus formation without the risk of bleeding or adverse autoimmune responses.
The researchers say the vaccine worked as well as clopidogrel.
“Many stroke patients don’t take their blood thinning drugs as prescribed, which makes it more likely they will have another stroke,” said Hironori Nakagami, MD, of Osaka University Graduate School of Medicine in Japan.
“This vaccine might one day help solve this issue since it would only need to be injected periodically.”
Dr. Nakagami and his colleagues described the vaccine in Hypertension.
S100A9 had previously been reported to be a key molecule in the regulation of thrombus formation. The investigators therefore hypothesized that neutralizing S100A9 with a vaccine would provide sustained antithrombotic effects without increasing the risk of bleeding.
First, the researchers selected a region in S100A9 as a candidate target for the vaccine and conjugated it to keyhole limpet hemocyanin (KLH) as a carrier protein.
They also designed a S100A8 peptide vaccine. S100A8 forms a heterodimer with S100A9 but was not known to play a key role in thrombus formation.
The investigators then randomly assigned male C57BL/6J mice to receive either vaccine or KLH only as control.
The researchers vaccinated mice with S100A9 on days 0, 14, 28, and 126 with either 20 µg or 50 µg of S100A9 peptide. Other mice were vaccinated with S100A8 at a dose of 20 µg on days 0 and 14.
The vaccinated mice developed antibodies against either S100A8 or S100A9, the latter at the 50 µg dose of vaccine. The antibodies recognized the recombinant S100A8 and S100A9 without cross reactivity, which suggested specific binding of each induced antibody.
Assessing thrombus formation
The researchers examined the antithrombotic effects of S100A8 or S100A9 in mouse models of thrombotic middle cerebral artery (MCA) occlusion.
Twenty-one days after the final vaccination, mice immunized with S100A9 had significantly delayed MCA occlusion, with a greater antithrombotic effect in the 50 µg group.
This antithrombotic effect, the investigators said, was comparable to that observed in mice treated with clopidogrel at a dose of 6 mg/kg for 2 days.
The S100A8 vaccine did not prevent MCA occlusion, so the researchers focused on the S100A9 vaccine in subsequent experiments.
They studied the vaccine’s antithrombotic effects in a model of common carotid artery (CCA) occlusion and observed results similar to those seen in the MCA model.
Specifically, there was no significant difference in the CCA occlusion time between mice vaccinated with S100A9 and mice treated with clopidogrel.
The investigators also found the antithrombotic effect of the S100A9 vaccine lasted more than 2 months.
Post-stroke model
Dr. Nakagami and his colleagues then examined the antithrombotic effect of S100A9 in mice after a transient MCA stroke.
The researchers administered the S100A9 vaccine every 2 weeks, starting 1 week after the stroke, for a total of three times.
The vaccine induced anti-S100A9 antibodies, and the mice had significantly prolonged CCA occlusion times compared to KLH control mice. (The investigators said they assessed CCA occlusion because it was impossible to measure the regional cerebral blood flow after a transient MCA occlusion due to post-surgical cranial skin adhesions.)
This result suggested that S100A9 could prevent thrombus formation in mice that had already had a stroke.
Hemostatic parameters and safety
Additional experiments indicated that the S100A9 vaccine had no effect on hemostatic parameters as indicated by tail bleeding time, platelet count, activated partial thromboplastin time, and prothrombin time.
The researchers also evaluated the vaccine’s safety by examining immunologic responses.
Histological analysis at day 147 after the first immunization revealed no pathological changes, such as CD4+ T-cell infiltration or activation of F4/80+ microglia/macrophages.
The immunized mice had predominantly IgG1 responses. This indicated that the S100A9 vaccine selectively induced primary T helper 2 responses.
“We are continuing our research in hopes of being able to start clinical trials between 5 and 10 years from now, but there are differences between mice and humans in how the vaccine will be recognized by the immune system,” Dr. Nakagami explained.
“We should be able to overcome such problems and believe this vaccine provides a very promising strategy in secondary prevention of stroke.”
This research was funded by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Japan Cardiovascular Research Foundation, the SENSHIN Medical Research Foundation, and the Japan Agency for Medical Research and Development.
Dr. Nakagami and five of the eleven authors have applied for a patent for the S100A9 vaccine.
Dr. Nakagami and five other authors are affiliated with departments at Osaka University that receive financial support from AnGes, DAICEL, FunPep, Novartis, Shionogi, Boehringer, and Rohto. One author is a founder, stockholder, and former board member of AnGes.
Investigators designed an antiplatelet vaccine they say could be a novel therapy to prevent recurrent ischemic stroke.
The vaccine inhibits S100A9 (S100 calcium-binding protein A9)/CD36 (cluster of differentiation 36) signaling in platelets, which is a key signal in arterial thrombosis but not hemostasis.
Mice immunized with the vaccine experienced an antithrombotic effect that lasted 84 days.
The vaccine inhibited thrombus formation without the risk of bleeding or adverse autoimmune responses.
The researchers say the vaccine worked as well as clopidogrel.
“Many stroke patients don’t take their blood thinning drugs as prescribed, which makes it more likely they will have another stroke,” said Hironori Nakagami, MD, of Osaka University Graduate School of Medicine in Japan.
“This vaccine might one day help solve this issue since it would only need to be injected periodically.”
Dr. Nakagami and his colleagues described the vaccine in Hypertension.
S100A9 had previously been reported to be a key molecule in the regulation of thrombus formation. The investigators therefore hypothesized that neutralizing S100A9 with a vaccine would provide sustained antithrombotic effects without increasing the risk of bleeding.
First, the researchers selected a region in S100A9 as a candidate target for the vaccine and conjugated it to keyhole limpet hemocyanin (KLH) as a carrier protein.
They also designed a S100A8 peptide vaccine. S100A8 forms a heterodimer with S100A9 but was not known to play a key role in thrombus formation.
The investigators then randomly assigned male C57BL/6J mice to receive either vaccine or KLH only as control.
The researchers vaccinated mice with S100A9 on days 0, 14, 28, and 126 with either 20 µg or 50 µg of S100A9 peptide. Other mice were vaccinated with S100A8 at a dose of 20 µg on days 0 and 14.
The vaccinated mice developed antibodies against either S100A8 or S100A9, the latter at the 50 µg dose of vaccine. The antibodies recognized the recombinant S100A8 and S100A9 without cross reactivity, which suggested specific binding of each induced antibody.
Assessing thrombus formation
The researchers examined the antithrombotic effects of S100A8 or S100A9 in mouse models of thrombotic middle cerebral artery (MCA) occlusion.
Twenty-one days after the final vaccination, mice immunized with S100A9 had significantly delayed MCA occlusion, with a greater antithrombotic effect in the 50 µg group.
This antithrombotic effect, the investigators said, was comparable to that observed in mice treated with clopidogrel at a dose of 6 mg/kg for 2 days.
The S100A8 vaccine did not prevent MCA occlusion, so the researchers focused on the S100A9 vaccine in subsequent experiments.
They studied the vaccine’s antithrombotic effects in a model of common carotid artery (CCA) occlusion and observed results similar to those seen in the MCA model.
Specifically, there was no significant difference in the CCA occlusion time between mice vaccinated with S100A9 and mice treated with clopidogrel.
The investigators also found the antithrombotic effect of the S100A9 vaccine lasted more than 2 months.
Post-stroke model
Dr. Nakagami and his colleagues then examined the antithrombotic effect of S100A9 in mice after a transient MCA stroke.
The researchers administered the S100A9 vaccine every 2 weeks, starting 1 week after the stroke, for a total of three times.
The vaccine induced anti-S100A9 antibodies, and the mice had significantly prolonged CCA occlusion times compared to KLH control mice. (The investigators said they assessed CCA occlusion because it was impossible to measure the regional cerebral blood flow after a transient MCA occlusion due to post-surgical cranial skin adhesions.)
This result suggested that S100A9 could prevent thrombus formation in mice that had already had a stroke.
Hemostatic parameters and safety
Additional experiments indicated that the S100A9 vaccine had no effect on hemostatic parameters as indicated by tail bleeding time, platelet count, activated partial thromboplastin time, and prothrombin time.
The researchers also evaluated the vaccine’s safety by examining immunologic responses.
Histological analysis at day 147 after the first immunization revealed no pathological changes, such as CD4+ T-cell infiltration or activation of F4/80+ microglia/macrophages.
The immunized mice had predominantly IgG1 responses. This indicated that the S100A9 vaccine selectively induced primary T helper 2 responses.
“We are continuing our research in hopes of being able to start clinical trials between 5 and 10 years from now, but there are differences between mice and humans in how the vaccine will be recognized by the immune system,” Dr. Nakagami explained.
“We should be able to overcome such problems and believe this vaccine provides a very promising strategy in secondary prevention of stroke.”
This research was funded by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Japan Cardiovascular Research Foundation, the SENSHIN Medical Research Foundation, and the Japan Agency for Medical Research and Development.
Dr. Nakagami and five of the eleven authors have applied for a patent for the S100A9 vaccine.
Dr. Nakagami and five other authors are affiliated with departments at Osaka University that receive financial support from AnGes, DAICEL, FunPep, Novartis, Shionogi, Boehringer, and Rohto. One author is a founder, stockholder, and former board member of AnGes.
Investigators designed an antiplatelet vaccine they say could be a novel therapy to prevent recurrent ischemic stroke.
The vaccine inhibits S100A9 (S100 calcium-binding protein A9)/CD36 (cluster of differentiation 36) signaling in platelets, which is a key signal in arterial thrombosis but not hemostasis.
Mice immunized with the vaccine experienced an antithrombotic effect that lasted 84 days.
The vaccine inhibited thrombus formation without the risk of bleeding or adverse autoimmune responses.
The researchers say the vaccine worked as well as clopidogrel.
“Many stroke patients don’t take their blood thinning drugs as prescribed, which makes it more likely they will have another stroke,” said Hironori Nakagami, MD, of Osaka University Graduate School of Medicine in Japan.
“This vaccine might one day help solve this issue since it would only need to be injected periodically.”
Dr. Nakagami and his colleagues described the vaccine in Hypertension.
S100A9 had previously been reported to be a key molecule in the regulation of thrombus formation. The investigators therefore hypothesized that neutralizing S100A9 with a vaccine would provide sustained antithrombotic effects without increasing the risk of bleeding.
First, the researchers selected a region in S100A9 as a candidate target for the vaccine and conjugated it to keyhole limpet hemocyanin (KLH) as a carrier protein.
They also designed a S100A8 peptide vaccine. S100A8 forms a heterodimer with S100A9 but was not known to play a key role in thrombus formation.
The investigators then randomly assigned male C57BL/6J mice to receive either vaccine or KLH only as control.
The researchers vaccinated mice with S100A9 on days 0, 14, 28, and 126 with either 20 µg or 50 µg of S100A9 peptide. Other mice were vaccinated with S100A8 at a dose of 20 µg on days 0 and 14.
The vaccinated mice developed antibodies against either S100A8 or S100A9, the latter at the 50 µg dose of vaccine. The antibodies recognized the recombinant S100A8 and S100A9 without cross reactivity, which suggested specific binding of each induced antibody.
Assessing thrombus formation
The researchers examined the antithrombotic effects of S100A8 or S100A9 in mouse models of thrombotic middle cerebral artery (MCA) occlusion.
Twenty-one days after the final vaccination, mice immunized with S100A9 had significantly delayed MCA occlusion, with a greater antithrombotic effect in the 50 µg group.
This antithrombotic effect, the investigators said, was comparable to that observed in mice treated with clopidogrel at a dose of 6 mg/kg for 2 days.
The S100A8 vaccine did not prevent MCA occlusion, so the researchers focused on the S100A9 vaccine in subsequent experiments.
They studied the vaccine’s antithrombotic effects in a model of common carotid artery (CCA) occlusion and observed results similar to those seen in the MCA model.
Specifically, there was no significant difference in the CCA occlusion time between mice vaccinated with S100A9 and mice treated with clopidogrel.
The investigators also found the antithrombotic effect of the S100A9 vaccine lasted more than 2 months.
Post-stroke model
Dr. Nakagami and his colleagues then examined the antithrombotic effect of S100A9 in mice after a transient MCA stroke.
The researchers administered the S100A9 vaccine every 2 weeks, starting 1 week after the stroke, for a total of three times.
The vaccine induced anti-S100A9 antibodies, and the mice had significantly prolonged CCA occlusion times compared to KLH control mice. (The investigators said they assessed CCA occlusion because it was impossible to measure the regional cerebral blood flow after a transient MCA occlusion due to post-surgical cranial skin adhesions.)
This result suggested that S100A9 could prevent thrombus formation in mice that had already had a stroke.
Hemostatic parameters and safety
Additional experiments indicated that the S100A9 vaccine had no effect on hemostatic parameters as indicated by tail bleeding time, platelet count, activated partial thromboplastin time, and prothrombin time.
The researchers also evaluated the vaccine’s safety by examining immunologic responses.
Histological analysis at day 147 after the first immunization revealed no pathological changes, such as CD4+ T-cell infiltration or activation of F4/80+ microglia/macrophages.
The immunized mice had predominantly IgG1 responses. This indicated that the S100A9 vaccine selectively induced primary T helper 2 responses.
“We are continuing our research in hopes of being able to start clinical trials between 5 and 10 years from now, but there are differences between mice and humans in how the vaccine will be recognized by the immune system,” Dr. Nakagami explained.
“We should be able to overcome such problems and believe this vaccine provides a very promising strategy in secondary prevention of stroke.”
This research was funded by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Japan Cardiovascular Research Foundation, the SENSHIN Medical Research Foundation, and the Japan Agency for Medical Research and Development.
Dr. Nakagami and five of the eleven authors have applied for a patent for the S100A9 vaccine.
Dr. Nakagami and five other authors are affiliated with departments at Osaka University that receive financial support from AnGes, DAICEL, FunPep, Novartis, Shionogi, Boehringer, and Rohto. One author is a founder, stockholder, and former board member of AnGes.
Aberrant RNA editing linked to aggressive myeloma
Overly zealous editing of messenger RNA in multiple myeloma cells appears to contribute to myeloma pathogenesis, and is prognostic of poor outcomes, investigators contend.
Over-expression of RNA editing enzymes in the adenosine deaminases acting on RNA (ADAR) family, specifically ADAR1, lead to hyperediting of the multiple myeloma (MM) transcriptome that in turn appears related to a drug-resistant disease phenotype and worse prognosis, reported Phaik Ju Teoh, PhD, of the Cancer Science Institute of Singapore, and colleagues.
The investigators implicate aberrant editing of adenosine to inosine (A-to-I) in malignant plasma cells, and its effects on NEIL1, a gene that encodes proteins involved in base excision repair of DNA, as important mechanisms in multiple myeloma pathogenesis.
“To the best of our knowledge, this is the first report of ADAR1-mediated hypereditome being an independent prognostic factor. The compromised integrity of MM transcriptome drives oncogenic phenotypes, likely contributing to the disease pathogenesis. Our current work, therefore, recognizes the clear biological and clinical importance of A-to-I editing at both the whole-transcriptome and gene-specific level (NEIL1) in MM,” they wrote in Blood.
A-to-I editing is the most prevalent form of RNA editing in humans, and aberrant editing mediated by ADAR1 has recently been linked to the development of several different cancer types, the investigators noted.
To see whether this process may also be involved in multiple myeloma, the investigators examined whole blood or bone marrow samples from healthy volunteers and patients with multiple myeloma.
They first looked at gene-expression profiling in the control and multiple myeloma samples and found that ADAR1 was overexpressed in the multiple myeloma cells, compared with nonmalignant plasma cells. Additionally, they saw that, at the protein level, ADAR1 was expressed at higher levels in patients with newly diagnosed or relapsed disease, compared with patients with smoldering myeloma or monoclonal gammopathy of undetermined significance.
They next determined that ADAR1 directly regulates hyperediting of the MM transcriptome, evidenced by the observation of a significant increase in A-to-G editing in the newly diagnosed and relapsed myeloma samples, compared with normal plasma cells. They confirmed this finding by observing the effects of ADAR1 levels on editing events across the transcriptome.
The authors followed this observation with experiments to see whether RNA editing by ADAR1 contributes to oncogenesis in myeloma cells. They silenced its expression and found that growth rate slowed and that ADAR1 wild-type protein introduced into cells promoted growth and proliferation.
“As the rescue with mutant ADAR1 is incomplete, we do not discount potential nonediting effects in ADAR1-induced oncogenesis in vivo. Nevertheless, taking into consideration the collective results from both the in vitro and in vivo studies, the RNA editing function of ADAR1 is important for its oncogenic effects in myeloma,” they wrote.
In the final steps, they identified NEIL1 as an important target for editing in multiple myeloma and observed that the editing compromised the ability of the proteins produced by the gene to accurately repair DNA damage.
“Further demonstrating its vital contribution to disease aggressiveness, patients with high ADAR1 expression showed less responsiveness toward standard and novel therapies. Therefore, our findings implied that a disturbed editome mediated by ADAR1 overexpression is both clinically and functionally crucial in our disease setting, and that ADAR1 confers oncogenic properties in myeloma in an editing-dependent manner,” they wrote.
The study was supported by the National Research Foundation Singapore, the Singapore Ministry of Education, and the National University of Singapore. The authors reported having no competing financial interests.
SOURCE: Teoh PJ et al. Blood. 2018;132(12):1304-17.
Overly zealous editing of messenger RNA in multiple myeloma cells appears to contribute to myeloma pathogenesis, and is prognostic of poor outcomes, investigators contend.
Over-expression of RNA editing enzymes in the adenosine deaminases acting on RNA (ADAR) family, specifically ADAR1, lead to hyperediting of the multiple myeloma (MM) transcriptome that in turn appears related to a drug-resistant disease phenotype and worse prognosis, reported Phaik Ju Teoh, PhD, of the Cancer Science Institute of Singapore, and colleagues.
The investigators implicate aberrant editing of adenosine to inosine (A-to-I) in malignant plasma cells, and its effects on NEIL1, a gene that encodes proteins involved in base excision repair of DNA, as important mechanisms in multiple myeloma pathogenesis.
“To the best of our knowledge, this is the first report of ADAR1-mediated hypereditome being an independent prognostic factor. The compromised integrity of MM transcriptome drives oncogenic phenotypes, likely contributing to the disease pathogenesis. Our current work, therefore, recognizes the clear biological and clinical importance of A-to-I editing at both the whole-transcriptome and gene-specific level (NEIL1) in MM,” they wrote in Blood.
A-to-I editing is the most prevalent form of RNA editing in humans, and aberrant editing mediated by ADAR1 has recently been linked to the development of several different cancer types, the investigators noted.
To see whether this process may also be involved in multiple myeloma, the investigators examined whole blood or bone marrow samples from healthy volunteers and patients with multiple myeloma.
They first looked at gene-expression profiling in the control and multiple myeloma samples and found that ADAR1 was overexpressed in the multiple myeloma cells, compared with nonmalignant plasma cells. Additionally, they saw that, at the protein level, ADAR1 was expressed at higher levels in patients with newly diagnosed or relapsed disease, compared with patients with smoldering myeloma or monoclonal gammopathy of undetermined significance.
They next determined that ADAR1 directly regulates hyperediting of the MM transcriptome, evidenced by the observation of a significant increase in A-to-G editing in the newly diagnosed and relapsed myeloma samples, compared with normal plasma cells. They confirmed this finding by observing the effects of ADAR1 levels on editing events across the transcriptome.
The authors followed this observation with experiments to see whether RNA editing by ADAR1 contributes to oncogenesis in myeloma cells. They silenced its expression and found that growth rate slowed and that ADAR1 wild-type protein introduced into cells promoted growth and proliferation.
“As the rescue with mutant ADAR1 is incomplete, we do not discount potential nonediting effects in ADAR1-induced oncogenesis in vivo. Nevertheless, taking into consideration the collective results from both the in vitro and in vivo studies, the RNA editing function of ADAR1 is important for its oncogenic effects in myeloma,” they wrote.
In the final steps, they identified NEIL1 as an important target for editing in multiple myeloma and observed that the editing compromised the ability of the proteins produced by the gene to accurately repair DNA damage.
“Further demonstrating its vital contribution to disease aggressiveness, patients with high ADAR1 expression showed less responsiveness toward standard and novel therapies. Therefore, our findings implied that a disturbed editome mediated by ADAR1 overexpression is both clinically and functionally crucial in our disease setting, and that ADAR1 confers oncogenic properties in myeloma in an editing-dependent manner,” they wrote.
The study was supported by the National Research Foundation Singapore, the Singapore Ministry of Education, and the National University of Singapore. The authors reported having no competing financial interests.
SOURCE: Teoh PJ et al. Blood. 2018;132(12):1304-17.
Overly zealous editing of messenger RNA in multiple myeloma cells appears to contribute to myeloma pathogenesis, and is prognostic of poor outcomes, investigators contend.
Over-expression of RNA editing enzymes in the adenosine deaminases acting on RNA (ADAR) family, specifically ADAR1, lead to hyperediting of the multiple myeloma (MM) transcriptome that in turn appears related to a drug-resistant disease phenotype and worse prognosis, reported Phaik Ju Teoh, PhD, of the Cancer Science Institute of Singapore, and colleagues.
The investigators implicate aberrant editing of adenosine to inosine (A-to-I) in malignant plasma cells, and its effects on NEIL1, a gene that encodes proteins involved in base excision repair of DNA, as important mechanisms in multiple myeloma pathogenesis.
“To the best of our knowledge, this is the first report of ADAR1-mediated hypereditome being an independent prognostic factor. The compromised integrity of MM transcriptome drives oncogenic phenotypes, likely contributing to the disease pathogenesis. Our current work, therefore, recognizes the clear biological and clinical importance of A-to-I editing at both the whole-transcriptome and gene-specific level (NEIL1) in MM,” they wrote in Blood.
A-to-I editing is the most prevalent form of RNA editing in humans, and aberrant editing mediated by ADAR1 has recently been linked to the development of several different cancer types, the investigators noted.
To see whether this process may also be involved in multiple myeloma, the investigators examined whole blood or bone marrow samples from healthy volunteers and patients with multiple myeloma.
They first looked at gene-expression profiling in the control and multiple myeloma samples and found that ADAR1 was overexpressed in the multiple myeloma cells, compared with nonmalignant plasma cells. Additionally, they saw that, at the protein level, ADAR1 was expressed at higher levels in patients with newly diagnosed or relapsed disease, compared with patients with smoldering myeloma or monoclonal gammopathy of undetermined significance.
They next determined that ADAR1 directly regulates hyperediting of the MM transcriptome, evidenced by the observation of a significant increase in A-to-G editing in the newly diagnosed and relapsed myeloma samples, compared with normal plasma cells. They confirmed this finding by observing the effects of ADAR1 levels on editing events across the transcriptome.
The authors followed this observation with experiments to see whether RNA editing by ADAR1 contributes to oncogenesis in myeloma cells. They silenced its expression and found that growth rate slowed and that ADAR1 wild-type protein introduced into cells promoted growth and proliferation.
“As the rescue with mutant ADAR1 is incomplete, we do not discount potential nonediting effects in ADAR1-induced oncogenesis in vivo. Nevertheless, taking into consideration the collective results from both the in vitro and in vivo studies, the RNA editing function of ADAR1 is important for its oncogenic effects in myeloma,” they wrote.
In the final steps, they identified NEIL1 as an important target for editing in multiple myeloma and observed that the editing compromised the ability of the proteins produced by the gene to accurately repair DNA damage.
“Further demonstrating its vital contribution to disease aggressiveness, patients with high ADAR1 expression showed less responsiveness toward standard and novel therapies. Therefore, our findings implied that a disturbed editome mediated by ADAR1 overexpression is both clinically and functionally crucial in our disease setting, and that ADAR1 confers oncogenic properties in myeloma in an editing-dependent manner,” they wrote.
The study was supported by the National Research Foundation Singapore, the Singapore Ministry of Education, and the National University of Singapore. The authors reported having no competing financial interests.
SOURCE: Teoh PJ et al. Blood. 2018;132(12):1304-17.
FROM BLOOD
Key clinical point:
Major finding: ADAR1-mediated editing of NEIL1 leads to a weakened DNA base excision repair mechanism.
Study details: Experimental series using plasma samples from healthy volunteers and patients with multiple myeloma.
Disclosures: The study was supported by the National Research Foundation Singapore, the Singapore Ministry of Education, and the National University of Singapore. The authors reported having no competing financial interests.
Source: Teoh PJ et al. Blood. 2018;132(12):1304-17.
FDA puts selinexor on fast track for DLBCL
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
You have ‘unique expertise’ to treat opioid use disorder in adolescents
ORLANDO – according to a presentation at the annual meeting of the American Academy of Pediatrics.
“We pediatricians have some unique skills that can really benefit our community of teens,” said Deepa Camenga, MD, of Yale University in New Haven, Conn.
Compared with some other specialists, who may be more reluctant to prescribe buprenorphine, pediatricians are more comfortable and have systems in place to deal with issues surrounding care coordination, adolescent confidentiality, family reassurance, and managing prescriptions for chronic diseases.“We can use those same skills when we’re caring for people with opioid use disorder,” she said.
According to the DSM-5 (Diagnostic and Statistical Manual–5), there are 11 criteria for opioid use disorder based on level of physiological dependence, impaired control, social functioning, and risky use. Meeting two or three criteria constitutes mild substance use disorder, while meeting six or more criteria is associated with severe substance use disorder.
Opioid use disorder in adolescents can be characterized by milder symptoms. Adolescents also tend to be in the early stage of this chronic disease when they seek care for opioid use disorder and need to be informed about the seriousness of the disease, Dr. Camenga noted.
“There is a disconnect about the severity of their illness when they present to me,” she said. “This is a disease that we know is chronic, severe – and without treatment – is progressive. We do know it can progress and get worse, and result in death.”
Treatment options for opioid use disorder in adolescents include behavioral interventions such as residential treatment, intensive outpatient (IOP), and partial hospitalization programs and therapy, as well as pharmacologic interventions like clonidine, buprenorphine, and methadone used for detoxification. Buprenorphine/naloxone has been labeled for use by patients 18 years or older; however, three recent randomized controlled trials have studied the effects of the intervention in 16-year-old and 17-year-old patients. In the trials, there were no serious adverse events reported with support of treatment for a minimum of 12 weeks and “many providers are treating up to a year” based on data from observational studies, Dr. Camenga said. Naltrexone also has been indicated for adolescents with opioid use disorder, with feasibility seen in pilot studies.
If you are interested in providing buprenorphine for patients, you need to apply for a Drug Enforcement Administration X-waiver, have access to their state’s prescription-monitoring program, and have a network of behavioral health providers for therapy and counseling, as well as psychiatrists for evaluation and treatment of other psychiatric disorders. Familiarity with naloxone overdose prevention training also is beneficial.
In addition, you must undergo 8 hours of training and apply for a waiver to prescribe buprenorphine in general medication settings. You can receive ongoing support after training on the AAP and Providers Clinical Support System websites.
Adolescent patients who receive buprenorphine for treatment of opioid use disorder typically undergo induction for 2 days where they are observed by a nurse or provider followed by weekly or biweekly medication-monitoring visits. It is “highly recommended” adolescents take urine drug screens during these visits but the results do not need to be observed. Many patients begin treatment when they are in IOP care, but some patients are not identified until they’ve had more severe consequences of opioid use disorder. Parents are involved in care by providing transportation and picking up and helping to administer medication, but there are confidential portions of the visits with the patient only.
“Parents have to be intimately involved and aware, and that’s an ideal situation,” Dr. Camenga said.
Dr. Camenga reported no relevant conflicts of interest.
ORLANDO – according to a presentation at the annual meeting of the American Academy of Pediatrics.
“We pediatricians have some unique skills that can really benefit our community of teens,” said Deepa Camenga, MD, of Yale University in New Haven, Conn.
Compared with some other specialists, who may be more reluctant to prescribe buprenorphine, pediatricians are more comfortable and have systems in place to deal with issues surrounding care coordination, adolescent confidentiality, family reassurance, and managing prescriptions for chronic diseases.“We can use those same skills when we’re caring for people with opioid use disorder,” she said.
According to the DSM-5 (Diagnostic and Statistical Manual–5), there are 11 criteria for opioid use disorder based on level of physiological dependence, impaired control, social functioning, and risky use. Meeting two or three criteria constitutes mild substance use disorder, while meeting six or more criteria is associated with severe substance use disorder.
Opioid use disorder in adolescents can be characterized by milder symptoms. Adolescents also tend to be in the early stage of this chronic disease when they seek care for opioid use disorder and need to be informed about the seriousness of the disease, Dr. Camenga noted.
“There is a disconnect about the severity of their illness when they present to me,” she said. “This is a disease that we know is chronic, severe – and without treatment – is progressive. We do know it can progress and get worse, and result in death.”
Treatment options for opioid use disorder in adolescents include behavioral interventions such as residential treatment, intensive outpatient (IOP), and partial hospitalization programs and therapy, as well as pharmacologic interventions like clonidine, buprenorphine, and methadone used for detoxification. Buprenorphine/naloxone has been labeled for use by patients 18 years or older; however, three recent randomized controlled trials have studied the effects of the intervention in 16-year-old and 17-year-old patients. In the trials, there were no serious adverse events reported with support of treatment for a minimum of 12 weeks and “many providers are treating up to a year” based on data from observational studies, Dr. Camenga said. Naltrexone also has been indicated for adolescents with opioid use disorder, with feasibility seen in pilot studies.
If you are interested in providing buprenorphine for patients, you need to apply for a Drug Enforcement Administration X-waiver, have access to their state’s prescription-monitoring program, and have a network of behavioral health providers for therapy and counseling, as well as psychiatrists for evaluation and treatment of other psychiatric disorders. Familiarity with naloxone overdose prevention training also is beneficial.
In addition, you must undergo 8 hours of training and apply for a waiver to prescribe buprenorphine in general medication settings. You can receive ongoing support after training on the AAP and Providers Clinical Support System websites.
Adolescent patients who receive buprenorphine for treatment of opioid use disorder typically undergo induction for 2 days where they are observed by a nurse or provider followed by weekly or biweekly medication-monitoring visits. It is “highly recommended” adolescents take urine drug screens during these visits but the results do not need to be observed. Many patients begin treatment when they are in IOP care, but some patients are not identified until they’ve had more severe consequences of opioid use disorder. Parents are involved in care by providing transportation and picking up and helping to administer medication, but there are confidential portions of the visits with the patient only.
“Parents have to be intimately involved and aware, and that’s an ideal situation,” Dr. Camenga said.
Dr. Camenga reported no relevant conflicts of interest.
ORLANDO – according to a presentation at the annual meeting of the American Academy of Pediatrics.
“We pediatricians have some unique skills that can really benefit our community of teens,” said Deepa Camenga, MD, of Yale University in New Haven, Conn.
Compared with some other specialists, who may be more reluctant to prescribe buprenorphine, pediatricians are more comfortable and have systems in place to deal with issues surrounding care coordination, adolescent confidentiality, family reassurance, and managing prescriptions for chronic diseases.“We can use those same skills when we’re caring for people with opioid use disorder,” she said.
According to the DSM-5 (Diagnostic and Statistical Manual–5), there are 11 criteria for opioid use disorder based on level of physiological dependence, impaired control, social functioning, and risky use. Meeting two or three criteria constitutes mild substance use disorder, while meeting six or more criteria is associated with severe substance use disorder.
Opioid use disorder in adolescents can be characterized by milder symptoms. Adolescents also tend to be in the early stage of this chronic disease when they seek care for opioid use disorder and need to be informed about the seriousness of the disease, Dr. Camenga noted.
“There is a disconnect about the severity of their illness when they present to me,” she said. “This is a disease that we know is chronic, severe – and without treatment – is progressive. We do know it can progress and get worse, and result in death.”
Treatment options for opioid use disorder in adolescents include behavioral interventions such as residential treatment, intensive outpatient (IOP), and partial hospitalization programs and therapy, as well as pharmacologic interventions like clonidine, buprenorphine, and methadone used for detoxification. Buprenorphine/naloxone has been labeled for use by patients 18 years or older; however, three recent randomized controlled trials have studied the effects of the intervention in 16-year-old and 17-year-old patients. In the trials, there were no serious adverse events reported with support of treatment for a minimum of 12 weeks and “many providers are treating up to a year” based on data from observational studies, Dr. Camenga said. Naltrexone also has been indicated for adolescents with opioid use disorder, with feasibility seen in pilot studies.
If you are interested in providing buprenorphine for patients, you need to apply for a Drug Enforcement Administration X-waiver, have access to their state’s prescription-monitoring program, and have a network of behavioral health providers for therapy and counseling, as well as psychiatrists for evaluation and treatment of other psychiatric disorders. Familiarity with naloxone overdose prevention training also is beneficial.
In addition, you must undergo 8 hours of training and apply for a waiver to prescribe buprenorphine in general medication settings. You can receive ongoing support after training on the AAP and Providers Clinical Support System websites.
Adolescent patients who receive buprenorphine for treatment of opioid use disorder typically undergo induction for 2 days where they are observed by a nurse or provider followed by weekly or biweekly medication-monitoring visits. It is “highly recommended” adolescents take urine drug screens during these visits but the results do not need to be observed. Many patients begin treatment when they are in IOP care, but some patients are not identified until they’ve had more severe consequences of opioid use disorder. Parents are involved in care by providing transportation and picking up and helping to administer medication, but there are confidential portions of the visits with the patient only.
“Parents have to be intimately involved and aware, and that’s an ideal situation,” Dr. Camenga said.
Dr. Camenga reported no relevant conflicts of interest.
EXPERT ANALYSIS AT AAP 18
Some statins worse than others for musculoskeletal adverse event onset time
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
FROM PHARMACOLOGY RESEARCH & PERSPECTIVES
Concerns over discretion, efficacy lead teen females to use emergency contraception
Emergency contraception is perceived as “easy, effective, and discrete,” especially when compared with nonemergent contraception and condoms, according to a qualitative study of contraceptive behaviors and decision making among adolescent females who had previously used emergency contraception (EC) or planned to use it.
“Three main themes emerged from our interviews: There are multiple perceived benefits to using EC, nonemergent contraception (NEC) use is challenging, and the decision to use NEC is multifactorial,” lead author Geetha N. Fink, MD, MPH, and her coauthors wrote in the Journal of Pediatric and Adolescent Gynecology.
The investigators reviewed interview transcripts and questionnaire responses from 28 adolescent females who had all used or were planning to use EC. The participants, who were recruited from school-based health centers (SBHC) in New York, reported having used EC a mean of 3.5 times (range 0-30 times), noted Dr. Fink of the department of obstetrics, gynecology and reproductive sciences at the Icahn School of Medicine at Mount Sinai in New York and her colleagues.
SBHCs in New York can distribute EC for free and – once general consent to care at the SBHC is provided at the start of each school year– without parental notification. This ease of access contributed to EC use, along with its minimal side effects. EC also can “be used discretely without the involvement of the partner,” Dr. Fink and her coauthors noted. Although the majority of participants stated being comfortable discussing their EC use, “they still appreciated that EC does not require partner involvement or awareness, unlike condoms or withdrawal.”
The participants’ decision making often was influenced by misperception; 65% incorrectly stated that EC was 90%-99% effective, and NEC use was ascribed to beliefs that “excess EC decreases efficacy or is detrimental to health and social interactions.” At the same time, Dr. Fink and her colleagues found that NEC use was associated with participants who had more sexual experience or who correctly identified it as more effective than EC.
“Our findings suggest that as adolescents gained more experience with sex and counseling, and also matured, they appeared to be more likely to utilize NEC,” they wrote.
Dr. Fink and her associates shared limitations of their study, including the uniqueness of SBHCs in New York City in providing comprehensive health care options, compared with those in the rest of the United States. However, they also noted the value in interviewing adolescent EC users and therefore better understanding why they’ve made these contraceptive decisions.
“We suspect many more students would benefit from access to EC and the SBHC, but may be unaware of these resources. We recommend increased efforts to promote awareness of these resources in schools, especially incorporated into sexual education. EC should be readily available for all adolescents,” they wrote.
The study was funded through a grant from the Society of Family Planning. No conflicts of interest were reported.
SOURCE: Fink GN et al. J Pediatr Adolesc Gynecol. 2018. doi: 10.1016/j.jpag.2018.10.005.
This study was very well conducted and provides genuine insight into adolescents who access contraception and their views about the difference between emergency contraception and nonemergent contraception. It also highlights that we have so much more work to do, from a public health perspective, when it comes to educating youth about the efficacy of contraception. If young people who have easier access to emergency contraception still believe incorrect information, what about those people who have minimal access?
Catherine Cansino, MD, MPH , is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis. She was asked to comment on the article by Fink et al.
This study was very well conducted and provides genuine insight into adolescents who access contraception and their views about the difference between emergency contraception and nonemergent contraception. It also highlights that we have so much more work to do, from a public health perspective, when it comes to educating youth about the efficacy of contraception. If young people who have easier access to emergency contraception still believe incorrect information, what about those people who have minimal access?
Catherine Cansino, MD, MPH , is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis. She was asked to comment on the article by Fink et al.
This study was very well conducted and provides genuine insight into adolescents who access contraception and their views about the difference between emergency contraception and nonemergent contraception. It also highlights that we have so much more work to do, from a public health perspective, when it comes to educating youth about the efficacy of contraception. If young people who have easier access to emergency contraception still believe incorrect information, what about those people who have minimal access?
Catherine Cansino, MD, MPH , is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis. She was asked to comment on the article by Fink et al.
Emergency contraception is perceived as “easy, effective, and discrete,” especially when compared with nonemergent contraception and condoms, according to a qualitative study of contraceptive behaviors and decision making among adolescent females who had previously used emergency contraception (EC) or planned to use it.
“Three main themes emerged from our interviews: There are multiple perceived benefits to using EC, nonemergent contraception (NEC) use is challenging, and the decision to use NEC is multifactorial,” lead author Geetha N. Fink, MD, MPH, and her coauthors wrote in the Journal of Pediatric and Adolescent Gynecology.
The investigators reviewed interview transcripts and questionnaire responses from 28 adolescent females who had all used or were planning to use EC. The participants, who were recruited from school-based health centers (SBHC) in New York, reported having used EC a mean of 3.5 times (range 0-30 times), noted Dr. Fink of the department of obstetrics, gynecology and reproductive sciences at the Icahn School of Medicine at Mount Sinai in New York and her colleagues.
SBHCs in New York can distribute EC for free and – once general consent to care at the SBHC is provided at the start of each school year– without parental notification. This ease of access contributed to EC use, along with its minimal side effects. EC also can “be used discretely without the involvement of the partner,” Dr. Fink and her coauthors noted. Although the majority of participants stated being comfortable discussing their EC use, “they still appreciated that EC does not require partner involvement or awareness, unlike condoms or withdrawal.”
The participants’ decision making often was influenced by misperception; 65% incorrectly stated that EC was 90%-99% effective, and NEC use was ascribed to beliefs that “excess EC decreases efficacy or is detrimental to health and social interactions.” At the same time, Dr. Fink and her colleagues found that NEC use was associated with participants who had more sexual experience or who correctly identified it as more effective than EC.
“Our findings suggest that as adolescents gained more experience with sex and counseling, and also matured, they appeared to be more likely to utilize NEC,” they wrote.
Dr. Fink and her associates shared limitations of their study, including the uniqueness of SBHCs in New York City in providing comprehensive health care options, compared with those in the rest of the United States. However, they also noted the value in interviewing adolescent EC users and therefore better understanding why they’ve made these contraceptive decisions.
“We suspect many more students would benefit from access to EC and the SBHC, but may be unaware of these resources. We recommend increased efforts to promote awareness of these resources in schools, especially incorporated into sexual education. EC should be readily available for all adolescents,” they wrote.
The study was funded through a grant from the Society of Family Planning. No conflicts of interest were reported.
SOURCE: Fink GN et al. J Pediatr Adolesc Gynecol. 2018. doi: 10.1016/j.jpag.2018.10.005.
Emergency contraception is perceived as “easy, effective, and discrete,” especially when compared with nonemergent contraception and condoms, according to a qualitative study of contraceptive behaviors and decision making among adolescent females who had previously used emergency contraception (EC) or planned to use it.
“Three main themes emerged from our interviews: There are multiple perceived benefits to using EC, nonemergent contraception (NEC) use is challenging, and the decision to use NEC is multifactorial,” lead author Geetha N. Fink, MD, MPH, and her coauthors wrote in the Journal of Pediatric and Adolescent Gynecology.
The investigators reviewed interview transcripts and questionnaire responses from 28 adolescent females who had all used or were planning to use EC. The participants, who were recruited from school-based health centers (SBHC) in New York, reported having used EC a mean of 3.5 times (range 0-30 times), noted Dr. Fink of the department of obstetrics, gynecology and reproductive sciences at the Icahn School of Medicine at Mount Sinai in New York and her colleagues.
SBHCs in New York can distribute EC for free and – once general consent to care at the SBHC is provided at the start of each school year– without parental notification. This ease of access contributed to EC use, along with its minimal side effects. EC also can “be used discretely without the involvement of the partner,” Dr. Fink and her coauthors noted. Although the majority of participants stated being comfortable discussing their EC use, “they still appreciated that EC does not require partner involvement or awareness, unlike condoms or withdrawal.”
The participants’ decision making often was influenced by misperception; 65% incorrectly stated that EC was 90%-99% effective, and NEC use was ascribed to beliefs that “excess EC decreases efficacy or is detrimental to health and social interactions.” At the same time, Dr. Fink and her colleagues found that NEC use was associated with participants who had more sexual experience or who correctly identified it as more effective than EC.
“Our findings suggest that as adolescents gained more experience with sex and counseling, and also matured, they appeared to be more likely to utilize NEC,” they wrote.
Dr. Fink and her associates shared limitations of their study, including the uniqueness of SBHCs in New York City in providing comprehensive health care options, compared with those in the rest of the United States. However, they also noted the value in interviewing adolescent EC users and therefore better understanding why they’ve made these contraceptive decisions.
“We suspect many more students would benefit from access to EC and the SBHC, but may be unaware of these resources. We recommend increased efforts to promote awareness of these resources in schools, especially incorporated into sexual education. EC should be readily available for all adolescents,” they wrote.
The study was funded through a grant from the Society of Family Planning. No conflicts of interest were reported.
SOURCE: Fink GN et al. J Pediatr Adolesc Gynecol. 2018. doi: 10.1016/j.jpag.2018.10.005.
FROM THE JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY
Key clinical point: 65% of adolescent females who were interviewed incorrectly believed that emergency contraception is 90%-99% effective.
Major finding: Adolescents who use emergency contraception prefer it over nonemergent contraception because it is perceived as easy to use and a more private alternative.
Study details: A study of 28 interviews of adolescent females who self-reported emergency contraception use.
Disclosures: The study was funded through a grant from the Society of Family Planning. No conflicts of interest were reported.
Source: Fink GN et al. J Pediatr Adolesc Gynecol. 2018. doi: 10.1016/j.jpag.2018.10.005.