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MUC-1 vaccine associated with notable overall survival rates in breast cancer
“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).
Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.
“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.
Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
Study Methods and Results
Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.
Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.
The study’s primary endpoint was the residual cancer burden at the time of surgery.
Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.
While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.
In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).
The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”
The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).
Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
Ideas for Further Study of Tecemotide
“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.
Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”
Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.
“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).
Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.
“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.
Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
Study Methods and Results
Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.
Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.
The study’s primary endpoint was the residual cancer burden at the time of surgery.
Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.
While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.
In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).
The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”
The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).
Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
Ideas for Further Study of Tecemotide
“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.
Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”
Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.
“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).
Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.
“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.
Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
Study Methods and Results
Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.
Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.
The study’s primary endpoint was the residual cancer burden at the time of surgery.
Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.
While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.
In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).
The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”
The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).
Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
Ideas for Further Study of Tecemotide
“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.
Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”
Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in</metaDescription> <articlePDF/> <teaserImage/> <teaser>Patients with HER2-negative early breast cancer receive preoperative standard of care neoadjuvant treatment with or without tecemotide, in new study.</teaser> <title>MUC-1 vaccine associated with notable overall survival rates in breast cancer</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> <term>23</term> <term>6</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term>270</term> <term canonical="true">192</term> <term>232</term> <term>364</term> <term>240</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>MUC-1 vaccine associated with notable overall survival rates in breast cancer</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.</span> </p> <p>“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).<br/><br/>Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer. <br/><br/>“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview. <br/><br/>Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a <span class="Hyperlink"><a href="https://patents.justia.com/patent/10154970">patented method</a></span> of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.<br/><br/></p> <h2>Study Methods and Results</h2> <p>Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide. </p> <p>Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.<br/><br/>The study’s primary endpoint was the residual cancer burden at the time of surgery. <br/><br/>Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.<br/><br/>While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; <em>P</em> = .42; 40.5% vs 34.8%; <em>P</em> = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis. <br/><br/>In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; <em>P</em> = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; <em>P </em>= .008). <br/><br/>The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”<br/><br/>The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; <em>P </em>= .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; <em>P</em> = .016). <br/><br/>Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”<br/><br/></p> <h2>Ideas for Further Study of Tecemotide</h2> <p>“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.</p> <p>Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.” <br/><br/>Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ASCO 2024
December 2017: Click for Credit
Here are 5 articles in the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. When Is It Really Recurrent Strep Throat?
To take the posttest, go to: http://bit.ly/2lHFh8i
Expires September 21, 2018
2. Revised Bethesda System Resets Thyroid Malignancy Risks
To take the posttest, go to: http://bit.ly/2iSLOvM
Expires August 10, 2018
3. Tips for Avoiding Potentially Dangerous Patients
To take the posttest, go to: http://bit.ly/2lH1Fi7
Expires August 10, 2018
4. Study Findings Support Uncapping MELD Score
To take the posttest, go to: http://bit.ly/2xOA7sI
Expires September 12, 2018
5. 'Motivational Pharmacotherapy' Engages Latino Patients With Depression
To take the posttest, go to: http://bit.ly/2zs2ly4
Expires August 14, 2018
Here are 5 articles in the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. When Is It Really Recurrent Strep Throat?
To take the posttest, go to: http://bit.ly/2lHFh8i
Expires September 21, 2018
2. Revised Bethesda System Resets Thyroid Malignancy Risks
To take the posttest, go to: http://bit.ly/2iSLOvM
Expires August 10, 2018
3. Tips for Avoiding Potentially Dangerous Patients
To take the posttest, go to: http://bit.ly/2lH1Fi7
Expires August 10, 2018
4. Study Findings Support Uncapping MELD Score
To take the posttest, go to: http://bit.ly/2xOA7sI
Expires September 12, 2018
5. 'Motivational Pharmacotherapy' Engages Latino Patients With Depression
To take the posttest, go to: http://bit.ly/2zs2ly4
Expires August 14, 2018
Here are 5 articles in the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. When Is It Really Recurrent Strep Throat?
To take the posttest, go to: http://bit.ly/2lHFh8i
Expires September 21, 2018
2. Revised Bethesda System Resets Thyroid Malignancy Risks
To take the posttest, go to: http://bit.ly/2iSLOvM
Expires August 10, 2018
3. Tips for Avoiding Potentially Dangerous Patients
To take the posttest, go to: http://bit.ly/2lH1Fi7
Expires August 10, 2018
4. Study Findings Support Uncapping MELD Score
To take the posttest, go to: http://bit.ly/2xOA7sI
Expires September 12, 2018
5. 'Motivational Pharmacotherapy' Engages Latino Patients With Depression
To take the posttest, go to: http://bit.ly/2zs2ly4
Expires August 14, 2018
IV ketamine proves superior to active placebo in low, high doses
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
FROM THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Ketamine’s effect size and improvement from baseline depression scores showed significant separation from placebo in most analyses conducted in this study.
Data source: Multicenter, randomly controlled, double-blind study of 99 adults with treatment-resistant depression given active placebo or various doses of intravenous ketamine.
Disclosures: Dr. Papakostas is the scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute. This study’s coinvestigator, Dr. Maurizio Fava, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
‘Motivational pharmacotherapy’ engages Latino patients with depression
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Continuous glucose monitors aren’t just for abdomens anymore
Close to two-thirds of people with diabetes who wear a continuous glucose monitor position it on an area of the body other than the abdomen, the only site sanctioned by the device’s manufacturer and federal authorities. And that lack of compliance has resulted in no apparent ill effects, according to a new study of related social media.
Michelle L. Litchman, PhD, of the University of Utah in Salt Lake City, and her colleagues, examined nearly 3,000 online postings of photos of continuous glucose monitors (CGM) manufactured by Dexcom, currently the most popular brand of CGMs in the United States. The results of their study, presented at this year’s annual meeting of the American Association of Diabetes Educators, showed that about 74% of device-wearing patients place it on the upper arm, thigh, buttocks, or back, rather than the abdomen, as indicated by the Food and Drug Administration. The device is indicated for use on the abdomen in adults because that was the only location used for the clinical studies of the device, Dr. Litchman explained in an interview.
Overall, out of 2,923 Instagram posts concerning the Dexcom CGM device, Dr. Litchman and her fellow investigators culled 353 photos of the device being worn on the body. Of these, 26.1% indicated the device was placed according to FDA guidance, while 63.7% of the remaining photos depicted the device placed on the inner arm, the forearm, thigh, calf, buttock, or back. In just over 10% of the photos, the device’s location on the body was unclear. Dr. Litchman and her colleagues concluded that when the device was worn according to directions, the failure rate was 6.2%. When placed on the outer arm it had a 2.2% failure rate, and there was a 3.3% failure rate when the device was worn on the thigh.
Since the combined nonabdomen and abdomen failure rates were similar, Dr. Litchman suggested any noncompliance was simply pragmatism. Although the CGM is meant to be relocated weekly around the abdomen, that is also the area of the body typically used for insulin injections several times a day, often resulting in scar tissue build-up that lessens insulin absorption. “It boils down to how much real estate someone has for effective insulin administration,” Dr. Litchman noted. “Individuals with diabetes need to protect the sites where they will inject insulin for the rest of their lives.”
For tips on how to do this effectively, Dr. Litchman said people with diabetes increasingly turn to online communities.
“There are differences in the FDA-approved, by the book, information patients are given and what they do in real life. While some may view this as a threat, I like to see this as opportunity to learn from patients. Patients are finding successes outside of [official instructions], therefore, we should be seeking out this experiential evidence. This research is a start to better understanding the safety related to CGM use in sites other than the abdomen,” she said in the interview.
Dr. Litchman reported that she had no conflict of interest to disclose.
Close to two-thirds of people with diabetes who wear a continuous glucose monitor position it on an area of the body other than the abdomen, the only site sanctioned by the device’s manufacturer and federal authorities. And that lack of compliance has resulted in no apparent ill effects, according to a new study of related social media.
Michelle L. Litchman, PhD, of the University of Utah in Salt Lake City, and her colleagues, examined nearly 3,000 online postings of photos of continuous glucose monitors (CGM) manufactured by Dexcom, currently the most popular brand of CGMs in the United States. The results of their study, presented at this year’s annual meeting of the American Association of Diabetes Educators, showed that about 74% of device-wearing patients place it on the upper arm, thigh, buttocks, or back, rather than the abdomen, as indicated by the Food and Drug Administration. The device is indicated for use on the abdomen in adults because that was the only location used for the clinical studies of the device, Dr. Litchman explained in an interview.
Overall, out of 2,923 Instagram posts concerning the Dexcom CGM device, Dr. Litchman and her fellow investigators culled 353 photos of the device being worn on the body. Of these, 26.1% indicated the device was placed according to FDA guidance, while 63.7% of the remaining photos depicted the device placed on the inner arm, the forearm, thigh, calf, buttock, or back. In just over 10% of the photos, the device’s location on the body was unclear. Dr. Litchman and her colleagues concluded that when the device was worn according to directions, the failure rate was 6.2%. When placed on the outer arm it had a 2.2% failure rate, and there was a 3.3% failure rate when the device was worn on the thigh.
Since the combined nonabdomen and abdomen failure rates were similar, Dr. Litchman suggested any noncompliance was simply pragmatism. Although the CGM is meant to be relocated weekly around the abdomen, that is also the area of the body typically used for insulin injections several times a day, often resulting in scar tissue build-up that lessens insulin absorption. “It boils down to how much real estate someone has for effective insulin administration,” Dr. Litchman noted. “Individuals with diabetes need to protect the sites where they will inject insulin for the rest of their lives.”
For tips on how to do this effectively, Dr. Litchman said people with diabetes increasingly turn to online communities.
“There are differences in the FDA-approved, by the book, information patients are given and what they do in real life. While some may view this as a threat, I like to see this as opportunity to learn from patients. Patients are finding successes outside of [official instructions], therefore, we should be seeking out this experiential evidence. This research is a start to better understanding the safety related to CGM use in sites other than the abdomen,” she said in the interview.
Dr. Litchman reported that she had no conflict of interest to disclose.
Close to two-thirds of people with diabetes who wear a continuous glucose monitor position it on an area of the body other than the abdomen, the only site sanctioned by the device’s manufacturer and federal authorities. And that lack of compliance has resulted in no apparent ill effects, according to a new study of related social media.
Michelle L. Litchman, PhD, of the University of Utah in Salt Lake City, and her colleagues, examined nearly 3,000 online postings of photos of continuous glucose monitors (CGM) manufactured by Dexcom, currently the most popular brand of CGMs in the United States. The results of their study, presented at this year’s annual meeting of the American Association of Diabetes Educators, showed that about 74% of device-wearing patients place it on the upper arm, thigh, buttocks, or back, rather than the abdomen, as indicated by the Food and Drug Administration. The device is indicated for use on the abdomen in adults because that was the only location used for the clinical studies of the device, Dr. Litchman explained in an interview.
Overall, out of 2,923 Instagram posts concerning the Dexcom CGM device, Dr. Litchman and her fellow investigators culled 353 photos of the device being worn on the body. Of these, 26.1% indicated the device was placed according to FDA guidance, while 63.7% of the remaining photos depicted the device placed on the inner arm, the forearm, thigh, calf, buttock, or back. In just over 10% of the photos, the device’s location on the body was unclear. Dr. Litchman and her colleagues concluded that when the device was worn according to directions, the failure rate was 6.2%. When placed on the outer arm it had a 2.2% failure rate, and there was a 3.3% failure rate when the device was worn on the thigh.
Since the combined nonabdomen and abdomen failure rates were similar, Dr. Litchman suggested any noncompliance was simply pragmatism. Although the CGM is meant to be relocated weekly around the abdomen, that is also the area of the body typically used for insulin injections several times a day, often resulting in scar tissue build-up that lessens insulin absorption. “It boils down to how much real estate someone has for effective insulin administration,” Dr. Litchman noted. “Individuals with diabetes need to protect the sites where they will inject insulin for the rest of their lives.”
For tips on how to do this effectively, Dr. Litchman said people with diabetes increasingly turn to online communities.
“There are differences in the FDA-approved, by the book, information patients are given and what they do in real life. While some may view this as a threat, I like to see this as opportunity to learn from patients. Patients are finding successes outside of [official instructions], therefore, we should be seeking out this experiential evidence. This research is a start to better understanding the safety related to CGM use in sites other than the abdomen,” she said in the interview.
Dr. Litchman reported that she had no conflict of interest to disclose.
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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The abdomen may be only one of several sites appropriate for wearing a continuous glucose monitor.</metaDescription> <articlePDF/> <teaserImage>201208</teaserImage> <teaser>Personal photos of real-time continuous glucose monitors posted to online forums dedicated to diabetes management lead to questions about whether it’s time to expand best practices for their use. </teaser> <title>Continuous glucose monitors aren’t just for abdomens anymore</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels> <wireChannel>diabetes_endo_met</wireChannel> </wireChannels> <primaryCMSID/> <CMSIDs/> <keywords> <keyword>diabetes</keyword> <keyword> CGM</keyword> <keyword> social medical</keyword> </keywords> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>dbh</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>358</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">205</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240081f2.jpg</altRep> <description role="drol:caption">Dr. Michelle Litchman</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Continuous glucose monitors aren’t just for abdomens anymore</title> <deck/> </itemMeta> <itemContent> <p>Close to two-thirds of people with diabetes who wear a continuous glucose monitor position it on an area of the body other than the abdomen, the only site sanctioned by the device’s manufacturer and federal authorities. And that lack of compliance has resulted in no apparent ill effects, according to a new study of related social media.</p> <p><span class="Hyperlink"><a href="https://healthcare.utah.edu/fad/mddetail.php?physicianID=u0164002">Michelle L. Litchman, PhD</a></span>, of the University of Utah in Salt Lake City, and her colleagues, examined nearly 3,000 online postings of photos of continuous glucose monitors (CGM) manufactured by Dexcom, currently the most popular brand of CGMs in the United States. The results of their study, presented at this year’s annual meeting of the American Association of Diabetes Educators, showed that about 74% of device-wearing patients place it on the upper arm, thigh, buttocks, or back, rather than the abdomen, as indicated by the Food and Drug Administration. The device is indicated for use on the abdomen in adults because that was the only location used for the clinical studies of the device, Dr. Litchman explained in an interview.<br/><br/>[[{"fid":"201208","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Michelle Litchman, PhD, of the University of Utah, Salt Lake City","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Michelle Litchman"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]The FDA should consider approving CGMs for use elsewhere on the body, since based on the online comments of CGM users, the device’s sensor failed in 32 users and failure was equally likely to occur in people who used CGMs by the book as in those who wore it where they preferred to. Failure was described in the study as the device displaying blood sugar levels inaccurately, or in a “nonmeaningful” way. Typically, if a sensor fails, the wearer recalibrates it, or if necessary, replaces the device, often moving it to another place on the body. “Our research suggests people are wearing their CGM devices on areas other than the abdomen and don’t appear to be having problems,” Dr. Litchman said.<br/><br/>Overall, out of 2,923 Instagram posts concerning the Dexcom CGM device, Dr. Litchman and her fellow investigators culled 353 photos of the device being worn on the body. Of these, 26.1% indicated the device was placed according to FDA guidance, while 63.7% of the remaining photos depicted the device placed on the or inner arm, the forearm, thigh, calf, buttock, or back. In just over 10% of the photos, the device’s location on the body was unclear. Dr. Litchman and her colleagues concluded that when the device was worn according to directions, the failure rate was 6.2%. When placed on the outer arm it had a 2.2% failure rate, and there was a 3.3% failure rate when the device was worn on the thigh. <br/><br/>Since the combined nonabdomen and abdomen failure rates were similar, Dr. Litchman suggested any noncompliance was simply pragmatism. Although the CGM is meant to be relocated weekly around the abdomen, that is also the area of the body typically used for insulin injections several times a day, often resulting in scar tissue build-up that lessens insulin absorption. “It boils down to how much real estate someone has for effective insulin administration,” Dr. Litchman noted. “Individuals with diabetes need to protect the sites where they will inject insulin for the rest of their lives.”<br/><br/>For tips on how to do this effectively, Dr. Litchman said people with diabetes increasingly turn to online communities.<br/><br/>“There are differences in the FDA-approved, by the book, information patients are given and what they do in real life. While some may view this as a threat, I like to see this as opportunity to learn from patients. Patients are finding successes outside of [official instructions], therefore, we should be seeking out this experiential evidence. This research is a start to better understanding the safety related to CGM use in sites other than the abdomen,” she said in the interview. <br/><br/>Dr. Litchman reported that she had no conflict of interest to disclose.</p> <p class="email"><span class="Hyperlink"><a href="mailto:wmcknight%40frontlinemedcom.com?subject=">wmcknight@frontlinemedcom.com</a></span><br/><br/>On Twitter <span class="Hyperlink"><a href="http://twitter.com/whitneymcknight">@whitneymcknight</a></span></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>vitals</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p><strong>Key clinical point: </strong><span class="tag metaDescription">The abdomen may be only one of several sites appropriate for wearing a continuous glucose monitor.</span> <br/><br/><strong>Major finding: </strong>Over one quarter of continuous glucose monitors are worn successfully in a non-FDA-approved location on the body.<br/><br/><strong>Data source: </strong>Review of 353 photos posted online by persons with diabetes depicting them with the device worn elsewhere than the abdomen.<br/><br/><strong>Disclosures:</strong> Dr. Litchman reported she had no relevant disclosures.</p> </itemContent> </newsItem> </itemSet></root>
FROM AADE 2017
Key clinical point:
Major finding: Over one quarter of continuous glucose monitors are worn successfully in a non-FDA-approved location on the body.
Data source: Review of 353 photos posted online by persons with diabetes depicting them with the device worn elsewhere than the abdomen.
Disclosures: Dr. Litchman reported she had no relevant disclosures.
Senate confirms first mental health czar
The Senate has confirmed Elinore F. McCance-Katz, MD, PhD, as the nation’s first mental health czar.
Dr. McCance-Katz, a psychiatrist, has focused her career largely on addiction treatment, particularly opioid abuse. This expertise has helped her receive the backing of several mental health organizations, including the American Psychiatric Association, the National Alliance on Mental Illness, and the American Society of Addiction Medicine.
As leader of the Substance Abuse and Mental Health Services Administration, Dr. McCance-Katz is expected to streamline more than 100 federal mental health agencies into a more effective system and to oversee a more than $3.5 billion budget annually. Having previously served as SAMHSA’s chief medical officer, Dr. McCance-Katz once again enters the fray surrounding the agency’s historically poor record of serving people with serious mental illnesses such as schizophrenia and bipolar disorder. Dr. McCance-Katz stepped down from her chief medical officer role in 2015 after serving 2 years, later penning a piece criticizing the agency’s lack of commitment to understanding – much less implementing – psychiatric treatments based on a medical approach. Instead, she argued, SAMHSA favored non–evidence-based psychosocial interventions.
Despite this, Rep. Tim Murphy (R.-Penn.) – a clinical psychologist and the congressman most responsible for drafting the legislation that created the position – issued a highly critical statement when her nomination was announced earlier this year. He called into question Dr. McCance-Katz’s commitment to the medical model and blamed her in part for the agency’s previous failures.
Dr. McCance-Katz currently serves as the chief medical officer at the Rhode Island Department of Behavioral Healthcare, Developmental Disabilities, and Hospitals. She also is a professor of psychiatry and human behavior, and professor of behavioral and social sciences at Brown University, Providence, R.I. She is expected to take up her new post as U.S. assistant secretary for mental health and substance use by the fall, according to a SAMHSA spokeperson.
The Senate has confirmed Elinore F. McCance-Katz, MD, PhD, as the nation’s first mental health czar.
Dr. McCance-Katz, a psychiatrist, has focused her career largely on addiction treatment, particularly opioid abuse. This expertise has helped her receive the backing of several mental health organizations, including the American Psychiatric Association, the National Alliance on Mental Illness, and the American Society of Addiction Medicine.
As leader of the Substance Abuse and Mental Health Services Administration, Dr. McCance-Katz is expected to streamline more than 100 federal mental health agencies into a more effective system and to oversee a more than $3.5 billion budget annually. Having previously served as SAMHSA’s chief medical officer, Dr. McCance-Katz once again enters the fray surrounding the agency’s historically poor record of serving people with serious mental illnesses such as schizophrenia and bipolar disorder. Dr. McCance-Katz stepped down from her chief medical officer role in 2015 after serving 2 years, later penning a piece criticizing the agency’s lack of commitment to understanding – much less implementing – psychiatric treatments based on a medical approach. Instead, she argued, SAMHSA favored non–evidence-based psychosocial interventions.
Despite this, Rep. Tim Murphy (R.-Penn.) – a clinical psychologist and the congressman most responsible for drafting the legislation that created the position – issued a highly critical statement when her nomination was announced earlier this year. He called into question Dr. McCance-Katz’s commitment to the medical model and blamed her in part for the agency’s previous failures.
Dr. McCance-Katz currently serves as the chief medical officer at the Rhode Island Department of Behavioral Healthcare, Developmental Disabilities, and Hospitals. She also is a professor of psychiatry and human behavior, and professor of behavioral and social sciences at Brown University, Providence, R.I. She is expected to take up her new post as U.S. assistant secretary for mental health and substance use by the fall, according to a SAMHSA spokeperson.
The Senate has confirmed Elinore F. McCance-Katz, MD, PhD, as the nation’s first mental health czar.
Dr. McCance-Katz, a psychiatrist, has focused her career largely on addiction treatment, particularly opioid abuse. This expertise has helped her receive the backing of several mental health organizations, including the American Psychiatric Association, the National Alliance on Mental Illness, and the American Society of Addiction Medicine.
As leader of the Substance Abuse and Mental Health Services Administration, Dr. McCance-Katz is expected to streamline more than 100 federal mental health agencies into a more effective system and to oversee a more than $3.5 billion budget annually. Having previously served as SAMHSA’s chief medical officer, Dr. McCance-Katz once again enters the fray surrounding the agency’s historically poor record of serving people with serious mental illnesses such as schizophrenia and bipolar disorder. Dr. McCance-Katz stepped down from her chief medical officer role in 2015 after serving 2 years, later penning a piece criticizing the agency’s lack of commitment to understanding – much less implementing – psychiatric treatments based on a medical approach. Instead, she argued, SAMHSA favored non–evidence-based psychosocial interventions.
Despite this, Rep. Tim Murphy (R.-Penn.) – a clinical psychologist and the congressman most responsible for drafting the legislation that created the position – issued a highly critical statement when her nomination was announced earlier this year. He called into question Dr. McCance-Katz’s commitment to the medical model and blamed her in part for the agency’s previous failures.
Dr. McCance-Katz currently serves as the chief medical officer at the Rhode Island Department of Behavioral Healthcare, Developmental Disabilities, and Hospitals. She also is a professor of psychiatry and human behavior, and professor of behavioral and social sciences at Brown University, Providence, R.I. She is expected to take up her new post as U.S. assistant secretary for mental health and substance use by the fall, according to a SAMHSA spokeperson.
FDA approves faster, pangenotypic cure for hep C virus
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The AGA HCV Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
FDA approves faster, pangenotypic cure for hep C virus
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
The first pangenotypic treatment for the hepatitis C virus, which also shaves 4 weeks off current regimens, has just been approved by the Food and Drug Administration.
Manufactured by AbbVie, glecaprevir/pibrentasvir (Mavyret) combines a nonstructural protein 3/4A protease inhibitor with a next-generation NS5A protein inhibitor for a once-daily, ribavirin-free treatment for adults with any of the major genotypes of chronic hepatitis C virus (HCV) infection.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in a statement.
The 8-week regimen is indicated in patients without cirrhosis or with compensated cirrhosis, who are new to treatment, and those with limited treatment options, such as patients with chronic kidney disease, including those on dialysis. The intervention also is indicated in adults with HCV genotype 1 who have been treated with either of the drugs in the combination, but not both. Glecaprevir/pibrentasvir is not recommended in patients with moderate cirrhosis and is contraindicated in patients with severe cirrhosis and in those taking the drugs atazanavir and rifampin.
The safety and efficacy of the treatment were evaluated in approximately 2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis. In the clinical trials, between 92% and 100% of patients treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks had no detectable serum levels of the virus 12 weeks after finishing treatment. The most commonly reported adverse reactions were headache, fatigue, and nausea.
The FDA directs health care professionals to test all patients for current or prior hepatitis B virus (HBV) infection prior to starting this direct-acting antiviral drug combination since HBV reactivation has been reported in adult patients coinfected with both viruses who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy.
VIDEO: What role does autoimmune dysfunction play in schizophrenia?
SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.
“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”
Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.
In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.
The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.
“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”
On Twitter @whitneymcknight
SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.
“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”
Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.
In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.
The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.
“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”
On Twitter @whitneymcknight
SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.
“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”
Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.
In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.
The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.
“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”
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AT THE ICSR BIENNIAL MEETING
More treatments becoming available for tardive dyskinesia
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. 
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
EXPERT ANALYSIS FROM The ASCP ANNUAL MEETING
