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High Marks for New CAR T Toxicity Grading Tool
“Hematotoxicity after CAR T is common and clinically relevant, but it also remains poorly understood [with] a high degree of heterogeneity in terms of grading its clinical management,” said first author Kai Rejeski, MD, in presenting on the findings at the 6th European CAR T-cell Meeting, held in Spain and jointly sponsored by the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA).
“We hope that this novel grading system helps with this by enabling harmonized reporting using the same nomenclature and allowing the comparison of the expected incidence rates of grade 3 or higher [hematological toxicities] across several disease entities and CAR T products,” said Dr. Rejeski, of the Adult BMT (Blood Marrow Transplant) and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York City.
ICAHT Grading System
In a recent meta-analysis, Dr. Rejeski and his team found that infections are the cause of as many as 49% of non–relapse related deaths after CAR T-cell therapy, representing the most common cause of death and numbering significantly more than the more prominent causes of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity (ICANS), which paradoxically have been the focus of significantly more research. In addition, the authors have reported substantial inconsistency among CAR T centers in the grading and management of the post–CAR T cytopenias that can cause those infections, underscoring the need for better guidelines.
“The narrative around CAR T toxicity has long centered on CRS and ICANS as novel and prototypical side effects with distinct management protocols,” Dr. Rejeski said in an interview. “However, it is cytopenias and the associated infections that drive nonrelapse mortality after CAR T.”
To address the need, the EHA and EBMT established the grading system for Immune Effector Cell–Associated HematoToxicity (ICAHT) that is applicable across disease types, indications, and treatment settings.
The details of the grading system were published in September 2023 in the journal Blood. The new system, which specifically focuses on neutrophil count and timing, importantly addresses the biphasic nature of ICAHT by distinguishing “early” ICAHT, occurring within 30 days of the CAR T administration, and “late” ICAHT, occurring more that 30 days following the treatment.
By contrast, conventional grading scales for CAR T–related cytopenias, such as the Common Terminology Criteria for Adverse Events (CTCAE) scale, “neither reflect the unique quality of post–CAR T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia,” the authors report in the study.
Real-World Evaluation
To assess the ICAHT grading system’s relevance in a real-world clinical setting of CAR T-cell therapy recipients, Dr. Rejeski and colleagues conducted a multicenter observational study, published in January 2024 in Blood Advances.
The study involved 549 patients at 12 international CAR T centers treated with BCMA- or CD19- directed CAR T therapy for relapsed/refractory B-cell malignancies.
Of the patients, 112 were treated for multiple myeloma (MM), 334 for large B cell lymphoma (LBCL), and 103 for mantle cell lymphoma (MCL).
Using the grading system, grade 3 (severe) or 4 (life-threatening) ICAHT (n = 125), was found to be strongly associated with key factors including a cumulative duration of severe neutropenia (P < .0001), the presence of multilineage cytopenias, such as severe thrombocytopenia (90%, compared with 46% in nonsevere ICAHT) and severe anemia (92% vs 49%; both P < .001), as well as the use of platelet and red blood cell transfusions.
Grade 3 or higher ICAHT was more common in patients with MCL (28%), compared with LBCL (23%) and MM (15%).
Key factors at baseline that were independently associated with severe ICAHT after multivariate adjustment included the presence of bone marrow infiltration, increased serum LDH levels, elevated CAR-HEMATOTOX scores (all P < .001), and receipt of CD28z costimulatory domain products, including axi-cel or brexu-cel (P = .01).
Those with grade 3 or higher ICAHT scores had a significantly higher rate of severe infections, compared with lower ICAHT scores (49% vs 13%; P < .0001), as well as increased nonrelapse mortality (14% vs 4.5%; P < .0001), primarily attributable to fatal infections.
Survival outcomes were also worse with grade 3 or higher ICAHT, including significantly lower rates of 1-year progression-free survival (35% vs 51%) and 1-year overall survival (52% vs 73%; both P < .0001).
Grade 3 or higher ICAHT was also significantly associated with prolonged hospital stays (median 21 vs 16 days; P < .0001).
However, contrary to findings from some previous studies, the current study showed no association between ICAHT severity and the prior administration of autologous stem cell transplant.
The number of prior treatment lines was not associated with grade 3 or higher ICAHT. However, grade 3 or higher CRS was more common as a cotoxicity (15% vs 5% without severe ICAHT), as was severe ICANS (26% vs 13%; both P < .001).
Notably, ICAHT grading showed superiority in the prediction of severe infections, compared with CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant).
While mild to moderate toxicity after CAR T-cell therapy has been associated with more favorable outcomes, the poor survival rates associated with severe ICAHT “underscore that high-grade toxicity and inferior treatment outcomes often go hand-in-hand,” the authors write.
Conversely, “the patients with grade 1 or 2 ICAHT exhibited excellent treatment outcomes in our study,” they point out.
Recommendations in Clinical Practice
For clinical guidance, the ICAHT grading system provides best practice recommendations based on severity for diagnostic work-up and management, such as measures including use of granulocyte-colony stimulating factor (G-CSF), anti-infective prophylaxis and stem cell boosts.
The authors add that preinfusion scoring systems, including the CAR-HEMATOTOX prognostic score, may be optimized by ICAHT grading in terms of modeling for severe or life-threatening ICAHT as an important endpoint.
“We have had an absence of the standardized severity-based guidelines that we know very well for CRS and ICANS, both in terms of the diagnostic work-up and the grading but also the management,” Dr. Rejeski said at the meeting.
“We hope that the new ICAHT grading focuses future research efforts to not only understand this important side effect better, but also develop specific management strategies that mitigate the risk of infections in high-risk patients,” Dr. Rejeski added.
“The multiply validated CAR-HEMATOTOX score, assessed at time of lymphodepletion, may be helpful in this regard,” he added.
An accompanying editorial published with the guidelines underscored that “this is the first such guideline by a major organization and is a much-needed development for the management of this important CAR T-cell–associated toxicity.”
The improved standardized reporting of ICAHT “could also inform hematotoxicity management protocols,” said the editorial authors, David Qualls, MD, of the Memorial Sloan Kettering Cancer Center in New York City and Caron Jacobson, MD, of the Dana-Farber Cancer Institute, in Boston, Massachusetts.
“While providing comprehensive recommendations for ICAHT, the EHA/EBMT guidelines also highlight important gaps in our current knowledge of ICAHT, which are significant,” the editorial authors add.
Further commenting, Ulrich Jaeger, MD, a professor of hematology at the Medical University of Vienna, Vienna, Austria, agreed that the research fills an important need in post–CAR T-cell therapy management.
“Dr. Rejeski´s work is really seminal in the field and confirmed by validation cohorts in other centers,” he said in an interview. “I think the story is absolutely clear. It will be of increasing importance, with more patients surviving. [The system] will have to be adapted to novel indications as well.”
Dr. Rejeski disclosed ties with Kite/Gilead, Novartis, GMS/Celgene, and Pierre-Fabre. Jaeger reports relationships with Novartis, Gilead Sciences, Celgene/BMS, Janssen, Roche, Miltenyi Biotec, and Innovative Medicines Initiative.
“Hematotoxicity after CAR T is common and clinically relevant, but it also remains poorly understood [with] a high degree of heterogeneity in terms of grading its clinical management,” said first author Kai Rejeski, MD, in presenting on the findings at the 6th European CAR T-cell Meeting, held in Spain and jointly sponsored by the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA).
“We hope that this novel grading system helps with this by enabling harmonized reporting using the same nomenclature and allowing the comparison of the expected incidence rates of grade 3 or higher [hematological toxicities] across several disease entities and CAR T products,” said Dr. Rejeski, of the Adult BMT (Blood Marrow Transplant) and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York City.
ICAHT Grading System
In a recent meta-analysis, Dr. Rejeski and his team found that infections are the cause of as many as 49% of non–relapse related deaths after CAR T-cell therapy, representing the most common cause of death and numbering significantly more than the more prominent causes of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity (ICANS), which paradoxically have been the focus of significantly more research. In addition, the authors have reported substantial inconsistency among CAR T centers in the grading and management of the post–CAR T cytopenias that can cause those infections, underscoring the need for better guidelines.
“The narrative around CAR T toxicity has long centered on CRS and ICANS as novel and prototypical side effects with distinct management protocols,” Dr. Rejeski said in an interview. “However, it is cytopenias and the associated infections that drive nonrelapse mortality after CAR T.”
To address the need, the EHA and EBMT established the grading system for Immune Effector Cell–Associated HematoToxicity (ICAHT) that is applicable across disease types, indications, and treatment settings.
The details of the grading system were published in September 2023 in the journal Blood. The new system, which specifically focuses on neutrophil count and timing, importantly addresses the biphasic nature of ICAHT by distinguishing “early” ICAHT, occurring within 30 days of the CAR T administration, and “late” ICAHT, occurring more that 30 days following the treatment.
By contrast, conventional grading scales for CAR T–related cytopenias, such as the Common Terminology Criteria for Adverse Events (CTCAE) scale, “neither reflect the unique quality of post–CAR T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia,” the authors report in the study.
Real-World Evaluation
To assess the ICAHT grading system’s relevance in a real-world clinical setting of CAR T-cell therapy recipients, Dr. Rejeski and colleagues conducted a multicenter observational study, published in January 2024 in Blood Advances.
The study involved 549 patients at 12 international CAR T centers treated with BCMA- or CD19- directed CAR T therapy for relapsed/refractory B-cell malignancies.
Of the patients, 112 were treated for multiple myeloma (MM), 334 for large B cell lymphoma (LBCL), and 103 for mantle cell lymphoma (MCL).
Using the grading system, grade 3 (severe) or 4 (life-threatening) ICAHT (n = 125), was found to be strongly associated with key factors including a cumulative duration of severe neutropenia (P < .0001), the presence of multilineage cytopenias, such as severe thrombocytopenia (90%, compared with 46% in nonsevere ICAHT) and severe anemia (92% vs 49%; both P < .001), as well as the use of platelet and red blood cell transfusions.
Grade 3 or higher ICAHT was more common in patients with MCL (28%), compared with LBCL (23%) and MM (15%).
Key factors at baseline that were independently associated with severe ICAHT after multivariate adjustment included the presence of bone marrow infiltration, increased serum LDH levels, elevated CAR-HEMATOTOX scores (all P < .001), and receipt of CD28z costimulatory domain products, including axi-cel or brexu-cel (P = .01).
Those with grade 3 or higher ICAHT scores had a significantly higher rate of severe infections, compared with lower ICAHT scores (49% vs 13%; P < .0001), as well as increased nonrelapse mortality (14% vs 4.5%; P < .0001), primarily attributable to fatal infections.
Survival outcomes were also worse with grade 3 or higher ICAHT, including significantly lower rates of 1-year progression-free survival (35% vs 51%) and 1-year overall survival (52% vs 73%; both P < .0001).
Grade 3 or higher ICAHT was also significantly associated with prolonged hospital stays (median 21 vs 16 days; P < .0001).
However, contrary to findings from some previous studies, the current study showed no association between ICAHT severity and the prior administration of autologous stem cell transplant.
The number of prior treatment lines was not associated with grade 3 or higher ICAHT. However, grade 3 or higher CRS was more common as a cotoxicity (15% vs 5% without severe ICAHT), as was severe ICANS (26% vs 13%; both P < .001).
Notably, ICAHT grading showed superiority in the prediction of severe infections, compared with CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant).
While mild to moderate toxicity after CAR T-cell therapy has been associated with more favorable outcomes, the poor survival rates associated with severe ICAHT “underscore that high-grade toxicity and inferior treatment outcomes often go hand-in-hand,” the authors write.
Conversely, “the patients with grade 1 or 2 ICAHT exhibited excellent treatment outcomes in our study,” they point out.
Recommendations in Clinical Practice
For clinical guidance, the ICAHT grading system provides best practice recommendations based on severity for diagnostic work-up and management, such as measures including use of granulocyte-colony stimulating factor (G-CSF), anti-infective prophylaxis and stem cell boosts.
The authors add that preinfusion scoring systems, including the CAR-HEMATOTOX prognostic score, may be optimized by ICAHT grading in terms of modeling for severe or life-threatening ICAHT as an important endpoint.
“We have had an absence of the standardized severity-based guidelines that we know very well for CRS and ICANS, both in terms of the diagnostic work-up and the grading but also the management,” Dr. Rejeski said at the meeting.
“We hope that the new ICAHT grading focuses future research efforts to not only understand this important side effect better, but also develop specific management strategies that mitigate the risk of infections in high-risk patients,” Dr. Rejeski added.
“The multiply validated CAR-HEMATOTOX score, assessed at time of lymphodepletion, may be helpful in this regard,” he added.
An accompanying editorial published with the guidelines underscored that “this is the first such guideline by a major organization and is a much-needed development for the management of this important CAR T-cell–associated toxicity.”
The improved standardized reporting of ICAHT “could also inform hematotoxicity management protocols,” said the editorial authors, David Qualls, MD, of the Memorial Sloan Kettering Cancer Center in New York City and Caron Jacobson, MD, of the Dana-Farber Cancer Institute, in Boston, Massachusetts.
“While providing comprehensive recommendations for ICAHT, the EHA/EBMT guidelines also highlight important gaps in our current knowledge of ICAHT, which are significant,” the editorial authors add.
Further commenting, Ulrich Jaeger, MD, a professor of hematology at the Medical University of Vienna, Vienna, Austria, agreed that the research fills an important need in post–CAR T-cell therapy management.
“Dr. Rejeski´s work is really seminal in the field and confirmed by validation cohorts in other centers,” he said in an interview. “I think the story is absolutely clear. It will be of increasing importance, with more patients surviving. [The system] will have to be adapted to novel indications as well.”
Dr. Rejeski disclosed ties with Kite/Gilead, Novartis, GMS/Celgene, and Pierre-Fabre. Jaeger reports relationships with Novartis, Gilead Sciences, Celgene/BMS, Janssen, Roche, Miltenyi Biotec, and Innovative Medicines Initiative.
“Hematotoxicity after CAR T is common and clinically relevant, but it also remains poorly understood [with] a high degree of heterogeneity in terms of grading its clinical management,” said first author Kai Rejeski, MD, in presenting on the findings at the 6th European CAR T-cell Meeting, held in Spain and jointly sponsored by the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA).
“We hope that this novel grading system helps with this by enabling harmonized reporting using the same nomenclature and allowing the comparison of the expected incidence rates of grade 3 or higher [hematological toxicities] across several disease entities and CAR T products,” said Dr. Rejeski, of the Adult BMT (Blood Marrow Transplant) and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York City.
ICAHT Grading System
In a recent meta-analysis, Dr. Rejeski and his team found that infections are the cause of as many as 49% of non–relapse related deaths after CAR T-cell therapy, representing the most common cause of death and numbering significantly more than the more prominent causes of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity (ICANS), which paradoxically have been the focus of significantly more research. In addition, the authors have reported substantial inconsistency among CAR T centers in the grading and management of the post–CAR T cytopenias that can cause those infections, underscoring the need for better guidelines.
“The narrative around CAR T toxicity has long centered on CRS and ICANS as novel and prototypical side effects with distinct management protocols,” Dr. Rejeski said in an interview. “However, it is cytopenias and the associated infections that drive nonrelapse mortality after CAR T.”
To address the need, the EHA and EBMT established the grading system for Immune Effector Cell–Associated HematoToxicity (ICAHT) that is applicable across disease types, indications, and treatment settings.
The details of the grading system were published in September 2023 in the journal Blood. The new system, which specifically focuses on neutrophil count and timing, importantly addresses the biphasic nature of ICAHT by distinguishing “early” ICAHT, occurring within 30 days of the CAR T administration, and “late” ICAHT, occurring more that 30 days following the treatment.
By contrast, conventional grading scales for CAR T–related cytopenias, such as the Common Terminology Criteria for Adverse Events (CTCAE) scale, “neither reflect the unique quality of post–CAR T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia,” the authors report in the study.
Real-World Evaluation
To assess the ICAHT grading system’s relevance in a real-world clinical setting of CAR T-cell therapy recipients, Dr. Rejeski and colleagues conducted a multicenter observational study, published in January 2024 in Blood Advances.
The study involved 549 patients at 12 international CAR T centers treated with BCMA- or CD19- directed CAR T therapy for relapsed/refractory B-cell malignancies.
Of the patients, 112 were treated for multiple myeloma (MM), 334 for large B cell lymphoma (LBCL), and 103 for mantle cell lymphoma (MCL).
Using the grading system, grade 3 (severe) or 4 (life-threatening) ICAHT (n = 125), was found to be strongly associated with key factors including a cumulative duration of severe neutropenia (P < .0001), the presence of multilineage cytopenias, such as severe thrombocytopenia (90%, compared with 46% in nonsevere ICAHT) and severe anemia (92% vs 49%; both P < .001), as well as the use of platelet and red blood cell transfusions.
Grade 3 or higher ICAHT was more common in patients with MCL (28%), compared with LBCL (23%) and MM (15%).
Key factors at baseline that were independently associated with severe ICAHT after multivariate adjustment included the presence of bone marrow infiltration, increased serum LDH levels, elevated CAR-HEMATOTOX scores (all P < .001), and receipt of CD28z costimulatory domain products, including axi-cel or brexu-cel (P = .01).
Those with grade 3 or higher ICAHT scores had a significantly higher rate of severe infections, compared with lower ICAHT scores (49% vs 13%; P < .0001), as well as increased nonrelapse mortality (14% vs 4.5%; P < .0001), primarily attributable to fatal infections.
Survival outcomes were also worse with grade 3 or higher ICAHT, including significantly lower rates of 1-year progression-free survival (35% vs 51%) and 1-year overall survival (52% vs 73%; both P < .0001).
Grade 3 or higher ICAHT was also significantly associated with prolonged hospital stays (median 21 vs 16 days; P < .0001).
However, contrary to findings from some previous studies, the current study showed no association between ICAHT severity and the prior administration of autologous stem cell transplant.
The number of prior treatment lines was not associated with grade 3 or higher ICAHT. However, grade 3 or higher CRS was more common as a cotoxicity (15% vs 5% without severe ICAHT), as was severe ICANS (26% vs 13%; both P < .001).
Notably, ICAHT grading showed superiority in the prediction of severe infections, compared with CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant).
While mild to moderate toxicity after CAR T-cell therapy has been associated with more favorable outcomes, the poor survival rates associated with severe ICAHT “underscore that high-grade toxicity and inferior treatment outcomes often go hand-in-hand,” the authors write.
Conversely, “the patients with grade 1 or 2 ICAHT exhibited excellent treatment outcomes in our study,” they point out.
Recommendations in Clinical Practice
For clinical guidance, the ICAHT grading system provides best practice recommendations based on severity for diagnostic work-up and management, such as measures including use of granulocyte-colony stimulating factor (G-CSF), anti-infective prophylaxis and stem cell boosts.
The authors add that preinfusion scoring systems, including the CAR-HEMATOTOX prognostic score, may be optimized by ICAHT grading in terms of modeling for severe or life-threatening ICAHT as an important endpoint.
“We have had an absence of the standardized severity-based guidelines that we know very well for CRS and ICANS, both in terms of the diagnostic work-up and the grading but also the management,” Dr. Rejeski said at the meeting.
“We hope that the new ICAHT grading focuses future research efforts to not only understand this important side effect better, but also develop specific management strategies that mitigate the risk of infections in high-risk patients,” Dr. Rejeski added.
“The multiply validated CAR-HEMATOTOX score, assessed at time of lymphodepletion, may be helpful in this regard,” he added.
An accompanying editorial published with the guidelines underscored that “this is the first such guideline by a major organization and is a much-needed development for the management of this important CAR T-cell–associated toxicity.”
The improved standardized reporting of ICAHT “could also inform hematotoxicity management protocols,” said the editorial authors, David Qualls, MD, of the Memorial Sloan Kettering Cancer Center in New York City and Caron Jacobson, MD, of the Dana-Farber Cancer Institute, in Boston, Massachusetts.
“While providing comprehensive recommendations for ICAHT, the EHA/EBMT guidelines also highlight important gaps in our current knowledge of ICAHT, which are significant,” the editorial authors add.
Further commenting, Ulrich Jaeger, MD, a professor of hematology at the Medical University of Vienna, Vienna, Austria, agreed that the research fills an important need in post–CAR T-cell therapy management.
“Dr. Rejeski´s work is really seminal in the field and confirmed by validation cohorts in other centers,” he said in an interview. “I think the story is absolutely clear. It will be of increasing importance, with more patients surviving. [The system] will have to be adapted to novel indications as well.”
Dr. Rejeski disclosed ties with Kite/Gilead, Novartis, GMS/Celgene, and Pierre-Fabre. Jaeger reports relationships with Novartis, Gilead Sciences, Celgene/BMS, Janssen, Roche, Miltenyi Biotec, and Innovative Medicines Initiative.
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Melville</byline> <bylineText>NANCY MELVILLE</bylineText> <bylineFull>NANCY MELVILLE</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. 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>A new grading system designed to improve the assessment of hematological toxicities following chimeric antigen receptor (CAR) T-cell therapy shows utility for a</metaDescription> <articlePDF/> <teaserImage/> <teaser>A real-world study demonstrates the benefits of a new grading system to assess hematotoxicities across disease types following CAR T-cell therapies.</teaser> <title>High Marks for New CAR T Toxicity Grading Tool</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>hemn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">18</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term>59374</term> <term canonical="true">195</term> <term>61821</term> <term>243</term> <term>250</term> <term>341</term> <term>27442</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>High Marks for New CAR T Toxicity Grading Tool</title> <deck/> </itemMeta> <itemContent> <p class="Normal">FROM THE 6TH EUROPEAN CAR T-CELL MEETING</p> <p><span class="tag metaDescription">A new grading system designed to improve the assessment of hematological toxicities following chimeric antigen receptor (CAR) T-cell therapy shows utility for a real-world population, providing much-needed standardization and guidance for management of the potentially life-threatening events. </span><br/><br/>“Hematotoxicity after CAR T is common and clinically relevant, but it also remains poorly understood [with] a high degree of heterogeneity in terms of grading its clinical management,” said first author Kai Rejeski, MD, in presenting on the findings at the 6th European CAR T-cell Meeting, held in Spain and jointly sponsored by the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA).<br/><br/>“We hope that this novel grading system helps with this by enabling harmonized reporting using the same nomenclature and allowing the comparison of the expected incidence rates of grade 3 or higher [hematological toxicities] across several disease entities and CAR T products,” said Dr. Rejeski, of the Adult BMT (Blood Marrow Transplant) and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York City.</p> <h2>ICAHT Grading System</h2> <p>In a recent <span class="Hyperlink"><a href="https://ash.confex.com/ash/2023/webprogram/Paper187516.html">meta-analysis</a>, </span>Dr. Rejeski and his team found that infections are the cause of as many as 49% of non–relapse related deaths after CAR T-cell therapy, representing the most common cause of death and numbering significantly more than the more prominent causes of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity (ICANS), which paradoxically have been the focus of significantly more research. In addition, the authors have <span class="Hyperlink"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145722/">reported</a></span> substantial inconsistency among CAR T centers in the grading and management of the post–CAR T cytopenias that can cause those infections, underscoring the need for better guidelines.<br/><br/>“The narrative around CAR T toxicity has long centered on CRS and ICANS as novel and prototypical side effects with distinct management protocols,” Dr. Rejeski said in an interview. “However, it is cytopenias and the associated infections that drive nonrelapse mortality after CAR T.”<br/><br/>To address the need, the EHA and EBMT established the grading system for Immune Effector Cell–Associated HematoToxicity (ICAHT) that is applicable across disease types, indications, and treatment settings. <br/><br/>The details of the grading system were <span class="Hyperlink"><a href="https://ashpublications.org/blood/article/142/10/865/496185/Immune-effector-cell-associated-hematotoxicity-EHA">published in September</a></span> 2023 in the journal <em>Blood</em>. The new system, which specifically focuses on neutrophil count and timing, importantly addresses the biphasic nature of ICAHT by distinguishing “early” ICAHT, occurring within 30 days of the CAR T administration, and “late” ICAHT, occurring more that 30 days following the treatment.<br/><br/>By contrast, conventional grading scales for CAR T–related cytopenias, such as the Common Terminology Criteria for Adverse Events (CTCAE) scale, “neither reflect the unique quality of post–CAR T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia,” the authors report in the study.</p> <h2>Real-World Evaluation</h2> <p>To assess the ICAHT grading system’s relevance in a real-world clinical setting of CAR T-cell therapy recipients, Dr. Rejeski and colleagues conducted a multicenter observational study, <span class="Hyperlink"><a href="https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023011767/506970/Applying-the-EHA-EBMT-Grading-for-ICAHT-after-CAR">published in January</a></span> 2024 in <em>Blood Advances</em>.<br/><br/>The study involved 549 patients at 12 international CAR T centers treated with BCMA- or CD19- directed CAR T therapy for relapsed/refractory B-cell malignancies.<br/><br/>Of the patients, 112 were treated for multiple myeloma (MM), 334 for large B cell lymphoma (LBCL), and 103 for mantle cell lymphoma (MCL).<br/><br/>Using the grading system, grade 3 (severe) or 4 (life-threatening) ICAHT (n = 125), was found to be strongly associated with key factors including a cumulative duration of severe neutropenia (<em>P</em> < .0001), the presence of multilineage cytopenias, such as severe thrombocytopenia (90%, compared with 46% in nonsevere ICAHT) and severe anemia (92% vs 49%; both <em>P</em> < .001), as well as the use of platelet and red blood cell transfusions.<br/><br/>Grade 3 or higher ICAHT was more common in patients with MCL (28%), compared with LBCL (23%) and MM (15%).<br/><br/>Key factors at baseline that were independently associated with severe ICAHT after multivariate adjustment included the presence of bone marrow infiltration, increased serum LDH levels, elevated CAR-HEMATOTOX scores (all <em>P</em> < .001), and receipt of CD28z costimulatory domain products, including axi-cel or brexu-cel (<em>P</em> = .01).<br/><br/>Those with grade 3 or higher ICAHT scores had a significantly higher rate of severe infections, compared with lower ICAHT scores (49% vs 13%; <em>P</em> < .0001), as well as increased nonrelapse mortality (14% vs 4.5%; <em>P</em> < .0001), primarily attributable to fatal infections.<br/><br/>Survival outcomes were also worse with grade 3 or higher ICAHT, including significantly lower rates of 1-year progression-free survival (35% vs 51%) and 1-year overall survival (52% vs 73%; both <em>P</em> < .0001). <br/><br/>Grade 3 or higher ICAHT was also significantly associated with prolonged hospital stays (median 21 vs 16 days; <em>P</em> < .0001). <br/><br/>However, contrary to findings from some previous studies, the current study showed no association between ICAHT severity and the prior administration of autologous stem cell transplant.<br/><br/>The number of prior treatment lines was not associated with grade 3 or higher ICAHT. However, grade 3 or higher CRS was more common as a cotoxicity (15% vs 5% without severe ICAHT), as was severe ICANS (26% vs 13%; both <em>P</em> < .001).<br/><br/>Notably, ICAHT grading showed superiority in the prediction of severe infections, compared with CTCAE grading (c-index 0.73 vs 0.55, <em>P</em> < .0001 vs nonsignificant). <br/><br/>While mild to moderate toxicity after CAR T-cell therapy has been associated with more favorable outcomes, the poor survival rates associated with severe ICAHT “underscore that high-grade toxicity and inferior treatment outcomes often go hand-in-hand,” the authors write.<br/><br/>Conversely, “the patients with grade 1 or 2 ICAHT exhibited excellent treatment outcomes in our study,” they point out.</p> <h2>Recommendations in Clinical Practice</h2> <p>For clinical guidance, the <span class="Hyperlink"><a href="https://ashpublications.org/blood/article/142/10/865/496185/Immune-effector-cell-associated-hematotoxicity-EHA">ICAHT grading system</a></span> provides best practice recommendations based on severity for diagnostic work-up and management, such as measures including use of granulocyte-colony stimulating factor (G-CSF), anti-infective prophylaxis and stem cell boosts.<br/><br/>The authors add that preinfusion scoring systems, including the CAR-HEMATOTOX prognostic score, may be optimized by ICAHT grading in terms of modeling for severe or life-threatening ICAHT as an important endpoint.<br/><br/>“We have had an absence of the standardized severity-based guidelines that we know very well for CRS and ICANS, both in terms of the diagnostic work-up and the grading but also the management,” Dr. Rejeski said at the meeting.<br/><br/>“We hope that the new ICAHT grading focuses future research efforts to not only understand this important side effect better, but also develop specific management strategies that mitigate the risk of infections in high-risk patients,” Dr. Rejeski added. <br/><br/>“The multiply validated CAR-HEMATOTOX score, assessed at time of lymphodepletion, may be helpful in this regard,” he added.<br/><br/>An accompanying <span class="Hyperlink"><a href="https://ashpublications.org/blood/article/142/10/859/497740/A-road-map-for-navigating-CAR-T-hematotoxicity">editorial</a></span> published with the guidelines underscored that “this is the first such guideline by a major organization and is a much-needed development for the management of this important CAR T-cell–associated toxicity.”<br/><br/>The improved standardized reporting of ICAHT “could also inform hematotoxicity management protocols,” said the editorial authors, David Qualls, MD, of the Memorial Sloan Kettering Cancer Center in New York City and Caron Jacobson, MD, of the Dana-Farber Cancer Institute, in Boston, Massachusetts.<br/><br/>“While providing comprehensive recommendations for ICAHT, the EHA/EBMT guidelines also highlight important gaps in our current knowledge of ICAHT, which are significant,” the editorial authors add.<br/><br/>Further commenting, Ulrich Jaeger, MD, a professor of hematology at the Medical University of Vienna, Vienna, Austria, agreed that the research fills an important need in post–CAR T-cell therapy management.<br/><br/>“Dr. Rejeski´s work is really seminal in the field and confirmed by validation cohorts in other centers,” he said in an interview. “I think the story is absolutely clear. It will be of increasing importance, with more patients surviving. [The system] will have to be adapted to novel indications as well.”<br/><br/>Dr. Rejeski disclosed ties with Kite/Gilead, Novartis, GMS/Celgene, and Pierre-Fabre. Jaeger reports relationships with Novartis, Gilead Sciences, Celgene/BMS, Janssen, Roche, Miltenyi Biotec, and Innovative Medicines Initiative.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM THE 6TH EUROPEAN CAR T-CELL MEETING
Metformin linked to reductions in COVID-19 viral load
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
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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>Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according</metaDescription> <articlePDF/> <teaserImage/> <teaser>Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings. </teaser> <title>Metformin linked to reductions in COVID-19 viral load</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>idprac</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>icymicov</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">20</term> <term>21</term> <term>69586</term> <term>15</term> <term>34</term> </publications> <sections> <term>39313</term> <term canonical="true">53</term> </sections> <topics> <term canonical="true">72046</term> <term>205</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Metformin linked to reductions in COVID-19 viral load</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Treatment with the diabetes drug <span class="Hyperlink">metformin</span> shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2201662">COVID-OUT trial</a></span>.</span> These findings add to a multitude of benefits the drug has been shown to have in COVID infection.</p> <p>COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.<br/><br/>“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.<br/><br/></p> <h2>Study details</h2> <p>For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.</p> <p>A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to <span class="Hyperlink">ivermectin</span> 390-470 mcg/kg per day for 3 days (n = 187), <span class="Hyperlink">fluvoxamine</span> 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.<br/><br/>The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.<br/><br/>The patients had a median age of 46 years, and all had either overweight or <span class="Hyperlink">obesity</span>. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.<br/><br/>About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.<br/><br/>The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.<br/><br/>The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; <em>P</em> = .003).<br/><br/>An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.<br/><br/>Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).<br/><br/>The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.<br/><br/>No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.<br/><br/>The findings are consistent with results of other recent observational studies, including <span class="Hyperlink">research</span> showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.<br/><br/>The authors’ previous <span class="Hyperlink"><a href="https://www.medrxiv.org/content/10.1101/2022.12.21.22283753v1.article-info">analysis</a></span> looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.<br/><br/>Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in <span class="Hyperlink">influenza</span>, and more recently, RNA assays suggesting effects against other RNA viruses, including the <span class="Hyperlink">Zika</span> virus.<br/><br/>In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.<br/><br/>“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.<br/><br/></p> <h2>‘Data from other studies are conflicting’</h2> <p>Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.</p> <p>However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of <span class="Hyperlink">HIV</span>, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.<br/><br/>Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.<br/><br/>Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.<br/><br/>The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.</p> <p> <em>A version of this article originally appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/988556">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM CROI 2023
Aspirin linked to reduced bladder, breast cancer mortality
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cannabis misconceptions still common among MS clinicians
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
From CMSC 2020
Laser Therapies Inappropriate For First-Line Acne Treatment
ANAHEIM, CALIF. — Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said experts at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
“I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out,” he said.
Most of the claims are backed by some research—infrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give physicians pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:231–40).
“There were over 25 methods for assessing acne severity and 19 methods for counting lesions,” he said. “That makes comparing one study to another very difficult.”
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
“Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient,” Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is much more questionable, he said.
“What we have to ask ourselves is this—do we really want this for our patients? And what's the long-term effect? We don't know,” Dr. Garden said. “The approach is new, and at the moment I'm very uncomfortable with this.”
And then there is the cost of light-based therapies, which are far more expensive than a medical option.
“These are highly expensive cash procedures requiring multiple visits to the office,” Dr. Spencer said. “I think light-based therapy for acne represent one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head.”
Dr. Garden agreed. “It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients,” he said.
“But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no,” he asserted. “It's not worth it—not yet.”
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. — Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said experts at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
“I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out,” he said.
Most of the claims are backed by some research—infrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give physicians pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:231–40).
“There were over 25 methods for assessing acne severity and 19 methods for counting lesions,” he said. “That makes comparing one study to another very difficult.”
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
“Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient,” Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is much more questionable, he said.
“What we have to ask ourselves is this—do we really want this for our patients? And what's the long-term effect? We don't know,” Dr. Garden said. “The approach is new, and at the moment I'm very uncomfortable with this.”
And then there is the cost of light-based therapies, which are far more expensive than a medical option.
“These are highly expensive cash procedures requiring multiple visits to the office,” Dr. Spencer said. “I think light-based therapy for acne represent one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head.”
Dr. Garden agreed. “It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients,” he said.
“But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no,” he asserted. “It's not worth it—not yet.”
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. — Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said experts at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
“I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out,” he said.
Most of the claims are backed by some research—infrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give physicians pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:231–40).
“There were over 25 methods for assessing acne severity and 19 methods for counting lesions,” he said. “That makes comparing one study to another very difficult.”
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
“Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient,” Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is much more questionable, he said.
“What we have to ask ourselves is this—do we really want this for our patients? And what's the long-term effect? We don't know,” Dr. Garden said. “The approach is new, and at the moment I'm very uncomfortable with this.”
And then there is the cost of light-based therapies, which are far more expensive than a medical option.
“These are highly expensive cash procedures requiring multiple visits to the office,” Dr. Spencer said. “I think light-based therapy for acne represent one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head.”
Dr. Garden agreed. “It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients,” he said.
“But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no,” he asserted. “It's not worth it—not yet.”
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
Follow the 'Five Ps' for Smooth Skin Resurfacing : Mnemonic can be used to optimize outcomes and patient satisfaction after skin resurfacing procedures.
ANAHEIM, CALIF. Ablative laser resurfacing offers perhaps the most effective means for smoothing wrinkles and acne scars, but its success depends on the "five Ps": prepared patients, a good preop evaluation, pain control, a perfectly done procedure, and postop diligence, Suzanne L. Kilmer, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
Requiring just a single treatment, ablative laser resurfacing removes the epidermis in a first pass, thereby eliminating epidermal lesions and helping to decrease the risk for actinic keratoses and basal cell carcinomas.
To achieve the best possible outcome, however, it's important to pay attention to the details included in the five Ps, said Dr. Kilmer of the department of dermatology at the University of California, Davis.
Prepared Patients
"The consult is critical," Dr. Kilmer said. "Educated patients are going to be much better prepared for what they will be dealing with and will have more realistic expectations."
To help alleviate fear, Dr. Kilmer said she shows patients a video of the procedure (supplied by the manufacturer), along with typical before-and-after photosand not just the best cases. "I'll even show my worst," she said. "I'll also show photos to give them an idea of how they can expect to look in a couple of days, a couple of weeks, and as time goes on."
In addition to the informed consent form, patients receive handouts describing the procedure (including preop preparation and postop care) and risk/benefit options.
Preoperative Evaluation
Because hyperpigmentation is one of the most common problems in ablative laser resurfacing, patients' skin type should be checked for that tendency, Dr. Kilmer said.
If patients have acne or other scars, the shallow, dish-shaped scars tend to respond the best, although the treatment significantly improves most acne scars, she said.
Photos of patients should be taken preoperatively and at 1 week, 6 weeks, 36 months, and 1 year. Full-face shots as well as close-ups of all anatomical units should be taken with good lighting and consistent settings.
"I can't emphasize enough the need to document with photographs in various stages," Dr. Kilmer said. "It's amazing how often patients won't see much improvement or will say some spot wasn't there and you can look back and show them that it was."
Pain Medications
Dr. Kilmer recommended EMLA with hydration for pain control. Not only does it enhance comfort, she said, but it also enhances safety, with less superficial coagulative thermal damage and less prolonged erythema. Redness has a much shorter duration, and the tendency for hyperpigmentation decreases, she added.
Dr. Kilmer instructs her patients to begin with hot, soapy soaks for 15 minutes at home and then immediately apply the EMLA and cover with a plastic wrap. A second tube is applied when they come to the office.
Patients who have previously had cold sores receive antiviral medications, and they also get antiyeast pills because persistent itching and redness can represent a low-grade yeast infection.
Valium (510 mg) and oral nonsteroidals are also given around the clock for the first few days to relieve pain.
Perfectly Done Procedure
Dr. Kilmer said she typically treats in quadrants, with a first pass using slightly higher intensity because the epidermis is so hydrated. Feathering peripherally in the first pass is also important to prevent a stop and start line.
She advises wiping everywhere except the neck, jaw line, and hairline, and giving a lighter treatment to fair or thin-skinned patients, who should never be wiped on the lateral third of the cheek.
Treatment of the neck can have good results and helps blend the entire treatment area nicely, Dr. Kilmer said, but she emphasized that EMLA should be used for extra protection from thermal damage and the neck should never be wiped.
Postop Diligence
Dr. Kilmer emphasized the need to stay on top of any potential problems, such as contact dermatitis from unexpected sources. "Fabric softening agents and dryer sheets … tend to have perfume and dyes, which can really be a problem," she said. Use of topical steroids can help in such situations.
If scarring is suspected, treatment should be given right away. A bubbly reaction seen on the skin texture signals a scarring problem, and she advises physicians to consult with others and seek help.
Likewise, treatment of hyperpigmentation cases should be swift, and patients should get zinc oxide right away, with hydroquinones and Retin-A at about a month after treatment.
In the thousands of cases she's done, Dr. Kilmer said she's never seen hyperpigmentation become permanent. EMLA and hydration help provide a greater margin of safety, making ablative laser resurfacing a highly effective tool, she noted.
"There is great efficacy, and you definitely see tightening, so I would say this is the most predictable device we have for resurfacing or regeneration," Dr. Kilmer concluded.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. Ablative laser resurfacing offers perhaps the most effective means for smoothing wrinkles and acne scars, but its success depends on the "five Ps": prepared patients, a good preop evaluation, pain control, a perfectly done procedure, and postop diligence, Suzanne L. Kilmer, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
Requiring just a single treatment, ablative laser resurfacing removes the epidermis in a first pass, thereby eliminating epidermal lesions and helping to decrease the risk for actinic keratoses and basal cell carcinomas.
To achieve the best possible outcome, however, it's important to pay attention to the details included in the five Ps, said Dr. Kilmer of the department of dermatology at the University of California, Davis.
Prepared Patients
"The consult is critical," Dr. Kilmer said. "Educated patients are going to be much better prepared for what they will be dealing with and will have more realistic expectations."
To help alleviate fear, Dr. Kilmer said she shows patients a video of the procedure (supplied by the manufacturer), along with typical before-and-after photosand not just the best cases. "I'll even show my worst," she said. "I'll also show photos to give them an idea of how they can expect to look in a couple of days, a couple of weeks, and as time goes on."
In addition to the informed consent form, patients receive handouts describing the procedure (including preop preparation and postop care) and risk/benefit options.
Preoperative Evaluation
Because hyperpigmentation is one of the most common problems in ablative laser resurfacing, patients' skin type should be checked for that tendency, Dr. Kilmer said.
If patients have acne or other scars, the shallow, dish-shaped scars tend to respond the best, although the treatment significantly improves most acne scars, she said.
Photos of patients should be taken preoperatively and at 1 week, 6 weeks, 36 months, and 1 year. Full-face shots as well as close-ups of all anatomical units should be taken with good lighting and consistent settings.
"I can't emphasize enough the need to document with photographs in various stages," Dr. Kilmer said. "It's amazing how often patients won't see much improvement or will say some spot wasn't there and you can look back and show them that it was."
Pain Medications
Dr. Kilmer recommended EMLA with hydration for pain control. Not only does it enhance comfort, she said, but it also enhances safety, with less superficial coagulative thermal damage and less prolonged erythema. Redness has a much shorter duration, and the tendency for hyperpigmentation decreases, she added.
Dr. Kilmer instructs her patients to begin with hot, soapy soaks for 15 minutes at home and then immediately apply the EMLA and cover with a plastic wrap. A second tube is applied when they come to the office.
Patients who have previously had cold sores receive antiviral medications, and they also get antiyeast pills because persistent itching and redness can represent a low-grade yeast infection.
Valium (510 mg) and oral nonsteroidals are also given around the clock for the first few days to relieve pain.
Perfectly Done Procedure
Dr. Kilmer said she typically treats in quadrants, with a first pass using slightly higher intensity because the epidermis is so hydrated. Feathering peripherally in the first pass is also important to prevent a stop and start line.
She advises wiping everywhere except the neck, jaw line, and hairline, and giving a lighter treatment to fair or thin-skinned patients, who should never be wiped on the lateral third of the cheek.
Treatment of the neck can have good results and helps blend the entire treatment area nicely, Dr. Kilmer said, but she emphasized that EMLA should be used for extra protection from thermal damage and the neck should never be wiped.
Postop Diligence
Dr. Kilmer emphasized the need to stay on top of any potential problems, such as contact dermatitis from unexpected sources. "Fabric softening agents and dryer sheets … tend to have perfume and dyes, which can really be a problem," she said. Use of topical steroids can help in such situations.
If scarring is suspected, treatment should be given right away. A bubbly reaction seen on the skin texture signals a scarring problem, and she advises physicians to consult with others and seek help.
Likewise, treatment of hyperpigmentation cases should be swift, and patients should get zinc oxide right away, with hydroquinones and Retin-A at about a month after treatment.
In the thousands of cases she's done, Dr. Kilmer said she's never seen hyperpigmentation become permanent. EMLA and hydration help provide a greater margin of safety, making ablative laser resurfacing a highly effective tool, she noted.
"There is great efficacy, and you definitely see tightening, so I would say this is the most predictable device we have for resurfacing or regeneration," Dr. Kilmer concluded.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. Ablative laser resurfacing offers perhaps the most effective means for smoothing wrinkles and acne scars, but its success depends on the "five Ps": prepared patients, a good preop evaluation, pain control, a perfectly done procedure, and postop diligence, Suzanne L. Kilmer, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
Requiring just a single treatment, ablative laser resurfacing removes the epidermis in a first pass, thereby eliminating epidermal lesions and helping to decrease the risk for actinic keratoses and basal cell carcinomas.
To achieve the best possible outcome, however, it's important to pay attention to the details included in the five Ps, said Dr. Kilmer of the department of dermatology at the University of California, Davis.
Prepared Patients
"The consult is critical," Dr. Kilmer said. "Educated patients are going to be much better prepared for what they will be dealing with and will have more realistic expectations."
To help alleviate fear, Dr. Kilmer said she shows patients a video of the procedure (supplied by the manufacturer), along with typical before-and-after photosand not just the best cases. "I'll even show my worst," she said. "I'll also show photos to give them an idea of how they can expect to look in a couple of days, a couple of weeks, and as time goes on."
In addition to the informed consent form, patients receive handouts describing the procedure (including preop preparation and postop care) and risk/benefit options.
Preoperative Evaluation
Because hyperpigmentation is one of the most common problems in ablative laser resurfacing, patients' skin type should be checked for that tendency, Dr. Kilmer said.
If patients have acne or other scars, the shallow, dish-shaped scars tend to respond the best, although the treatment significantly improves most acne scars, she said.
Photos of patients should be taken preoperatively and at 1 week, 6 weeks, 36 months, and 1 year. Full-face shots as well as close-ups of all anatomical units should be taken with good lighting and consistent settings.
"I can't emphasize enough the need to document with photographs in various stages," Dr. Kilmer said. "It's amazing how often patients won't see much improvement or will say some spot wasn't there and you can look back and show them that it was."
Pain Medications
Dr. Kilmer recommended EMLA with hydration for pain control. Not only does it enhance comfort, she said, but it also enhances safety, with less superficial coagulative thermal damage and less prolonged erythema. Redness has a much shorter duration, and the tendency for hyperpigmentation decreases, she added.
Dr. Kilmer instructs her patients to begin with hot, soapy soaks for 15 minutes at home and then immediately apply the EMLA and cover with a plastic wrap. A second tube is applied when they come to the office.
Patients who have previously had cold sores receive antiviral medications, and they also get antiyeast pills because persistent itching and redness can represent a low-grade yeast infection.
Valium (510 mg) and oral nonsteroidals are also given around the clock for the first few days to relieve pain.
Perfectly Done Procedure
Dr. Kilmer said she typically treats in quadrants, with a first pass using slightly higher intensity because the epidermis is so hydrated. Feathering peripherally in the first pass is also important to prevent a stop and start line.
She advises wiping everywhere except the neck, jaw line, and hairline, and giving a lighter treatment to fair or thin-skinned patients, who should never be wiped on the lateral third of the cheek.
Treatment of the neck can have good results and helps blend the entire treatment area nicely, Dr. Kilmer said, but she emphasized that EMLA should be used for extra protection from thermal damage and the neck should never be wiped.
Postop Diligence
Dr. Kilmer emphasized the need to stay on top of any potential problems, such as contact dermatitis from unexpected sources. "Fabric softening agents and dryer sheets … tend to have perfume and dyes, which can really be a problem," she said. Use of topical steroids can help in such situations.
If scarring is suspected, treatment should be given right away. A bubbly reaction seen on the skin texture signals a scarring problem, and she advises physicians to consult with others and seek help.
Likewise, treatment of hyperpigmentation cases should be swift, and patients should get zinc oxide right away, with hydroquinones and Retin-A at about a month after treatment.
In the thousands of cases she's done, Dr. Kilmer said she's never seen hyperpigmentation become permanent. EMLA and hydration help provide a greater margin of safety, making ablative laser resurfacing a highly effective tool, she noted.
"There is great efficacy, and you definitely see tightening, so I would say this is the most predictable device we have for resurfacing or regeneration," Dr. Kilmer concluded.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
Injectable Silicone Called a Safe, Elegant Filler
ANAHEIM, CALIF. Liquid injectable silicone can be a highly effective means of tissue augmentation, especially for acne scarring and HIV-related lipoatrophy, Derek Jones, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
"This can be an ideal filler that is long lasting and cosmetically elegant," said Dr. Jones of the department of dermatology at the University of California, Los Angeles.
A "wealth of anecdotal data" indicates that liquid injectable silicone is safe and effective, but the following critical rules are key to its safe usage, he said:
▸ Use only pure, Food and Drug Administration-approved, injectable-grade liquid silicone; in the United States that means only Silikon-1000, made by Alcon Laboratories. The product has FDA approval for intraocular injection to treat retinal detachment, but it may be legally used off label, under the 1997 FDA modernization act that allowed medical devices to be used off label.
It's important to note, however, that the law prohibits advertisement of off-label uses, and malpractice insurance carriers have different policies regarding such uses.
▸ Adhere to a strict serial puncture microdroplet technique, defined as 0.01 cc injected into the immediate subdermal plane or deeper at 2- to 4-mm intervals, with no double pass in the same plane. Intradermal injection should be strongly avoided except among the most skilled practitioners.
The technique is necessary to allow a fibroproliferative response that develops around each microdroplet between treatments, not only causing each droplet to become anchored and less likely to drift but contributing to further augmentation, Dr. Jones said.
"This is an oil, and if you inject a lot all at once, it's like throwing olive oil on the floorit's going to spread out and track tissue planes along the path of least resistance," he said. "But the microdroplet technique addresses this problem."
▸ Inject only small volumes2 cc or less for lipoatrophy, or 0.5 cc or less for other indications. "Avoid the temptation to use larger volumes," Dr. Jones said, adding that injections should be spread out at intervals of at least 4 weeks.
In addition to these three critical rules, important considerations for silicone use include informing patients that liquid injectable silicone is permanent, and that its use is still investigational and likely to remain so for years. And, while patients can resume a normal routine immediately, they are advised to avoid activities that could predispose them to blunt trauma.
Dr. Jones demonstrated the injection technique on a patient with HIV-related facial lipoatrophy at the conference and said that most patients are highly pleased with the results.
Liquid silicone injections "really give an extraordinarily natural-appearing correction," he said. "When you touch the cheeks of these individuals, they feel nice, soft, and supple, and the injections really can restore subtle and refined facial contours."
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
This HIV patient shows lipoatrophy before his silicone treatment.
Augmentation with injectable silicone gives a natural-appearing correction. Photos courtesy Dr. Derek Jones
ANAHEIM, CALIF. Liquid injectable silicone can be a highly effective means of tissue augmentation, especially for acne scarring and HIV-related lipoatrophy, Derek Jones, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
"This can be an ideal filler that is long lasting and cosmetically elegant," said Dr. Jones of the department of dermatology at the University of California, Los Angeles.
A "wealth of anecdotal data" indicates that liquid injectable silicone is safe and effective, but the following critical rules are key to its safe usage, he said:
▸ Use only pure, Food and Drug Administration-approved, injectable-grade liquid silicone; in the United States that means only Silikon-1000, made by Alcon Laboratories. The product has FDA approval for intraocular injection to treat retinal detachment, but it may be legally used off label, under the 1997 FDA modernization act that allowed medical devices to be used off label.
It's important to note, however, that the law prohibits advertisement of off-label uses, and malpractice insurance carriers have different policies regarding such uses.
▸ Adhere to a strict serial puncture microdroplet technique, defined as 0.01 cc injected into the immediate subdermal plane or deeper at 2- to 4-mm intervals, with no double pass in the same plane. Intradermal injection should be strongly avoided except among the most skilled practitioners.
The technique is necessary to allow a fibroproliferative response that develops around each microdroplet between treatments, not only causing each droplet to become anchored and less likely to drift but contributing to further augmentation, Dr. Jones said.
"This is an oil, and if you inject a lot all at once, it's like throwing olive oil on the floorit's going to spread out and track tissue planes along the path of least resistance," he said. "But the microdroplet technique addresses this problem."
▸ Inject only small volumes2 cc or less for lipoatrophy, or 0.5 cc or less for other indications. "Avoid the temptation to use larger volumes," Dr. Jones said, adding that injections should be spread out at intervals of at least 4 weeks.
In addition to these three critical rules, important considerations for silicone use include informing patients that liquid injectable silicone is permanent, and that its use is still investigational and likely to remain so for years. And, while patients can resume a normal routine immediately, they are advised to avoid activities that could predispose them to blunt trauma.
Dr. Jones demonstrated the injection technique on a patient with HIV-related facial lipoatrophy at the conference and said that most patients are highly pleased with the results.
Liquid silicone injections "really give an extraordinarily natural-appearing correction," he said. "When you touch the cheeks of these individuals, they feel nice, soft, and supple, and the injections really can restore subtle and refined facial contours."
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
This HIV patient shows lipoatrophy before his silicone treatment.
Augmentation with injectable silicone gives a natural-appearing correction. Photos courtesy Dr. Derek Jones
ANAHEIM, CALIF. Liquid injectable silicone can be a highly effective means of tissue augmentation, especially for acne scarring and HIV-related lipoatrophy, Derek Jones, M.D., said at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
"This can be an ideal filler that is long lasting and cosmetically elegant," said Dr. Jones of the department of dermatology at the University of California, Los Angeles.
A "wealth of anecdotal data" indicates that liquid injectable silicone is safe and effective, but the following critical rules are key to its safe usage, he said:
▸ Use only pure, Food and Drug Administration-approved, injectable-grade liquid silicone; in the United States that means only Silikon-1000, made by Alcon Laboratories. The product has FDA approval for intraocular injection to treat retinal detachment, but it may be legally used off label, under the 1997 FDA modernization act that allowed medical devices to be used off label.
It's important to note, however, that the law prohibits advertisement of off-label uses, and malpractice insurance carriers have different policies regarding such uses.
▸ Adhere to a strict serial puncture microdroplet technique, defined as 0.01 cc injected into the immediate subdermal plane or deeper at 2- to 4-mm intervals, with no double pass in the same plane. Intradermal injection should be strongly avoided except among the most skilled practitioners.
The technique is necessary to allow a fibroproliferative response that develops around each microdroplet between treatments, not only causing each droplet to become anchored and less likely to drift but contributing to further augmentation, Dr. Jones said.
"This is an oil, and if you inject a lot all at once, it's like throwing olive oil on the floorit's going to spread out and track tissue planes along the path of least resistance," he said. "But the microdroplet technique addresses this problem."
▸ Inject only small volumes2 cc or less for lipoatrophy, or 0.5 cc or less for other indications. "Avoid the temptation to use larger volumes," Dr. Jones said, adding that injections should be spread out at intervals of at least 4 weeks.
In addition to these three critical rules, important considerations for silicone use include informing patients that liquid injectable silicone is permanent, and that its use is still investigational and likely to remain so for years. And, while patients can resume a normal routine immediately, they are advised to avoid activities that could predispose them to blunt trauma.
Dr. Jones demonstrated the injection technique on a patient with HIV-related facial lipoatrophy at the conference and said that most patients are highly pleased with the results.
Liquid silicone injections "really give an extraordinarily natural-appearing correction," he said. "When you touch the cheeks of these individuals, they feel nice, soft, and supple, and the injections really can restore subtle and refined facial contours."
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
This HIV patient shows lipoatrophy before his silicone treatment.
Augmentation with injectable silicone gives a natural-appearing correction. Photos courtesy Dr. Derek Jones
Light Therapies Inappropriate for First-Line Acne Tx
ANAHEIM, CALIF. Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said dermatologists at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation. The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
"I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out," he said.
Most of the claims are backed by some researchinfrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give dermatologists pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:23140).
"There were over 25 methods for assessing acne severity and 19 methods for counting lesions," he said. "That makes comparing one study to another very difficult."
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
"Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient," Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is far more questionable, he said.
"What we have to ask ourselves is thisdo we really want this for our patients? And what's the long-term effect? We don't know," he said. "The approach is new, and at the moment I'm very uncomfortable with this."
And then there is the cost of light-based therapies, which are far more expensive than a medical option. "These are highly expensive cash procedures requiring multiple visits to the office," Dr. Spencer said. "I think light-based therapy for acne represents one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head."
Dr. Garden agreed. "It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients," he said.
"But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no," he asserted. "It's not worth itnot yet."
SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said dermatologists at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation. The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
"I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out," he said.
Most of the claims are backed by some researchinfrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give dermatologists pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:23140).
"There were over 25 methods for assessing acne severity and 19 methods for counting lesions," he said. "That makes comparing one study to another very difficult."
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
"Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient," Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is far more questionable, he said.
"What we have to ask ourselves is thisdo we really want this for our patients? And what's the long-term effect? We don't know," he said. "The approach is new, and at the moment I'm very uncomfortable with this."
And then there is the cost of light-based therapies, which are far more expensive than a medical option. "These are highly expensive cash procedures requiring multiple visits to the office," Dr. Spencer said. "I think light-based therapy for acne represents one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head."
Dr. Garden agreed. "It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients," he said.
"But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no," he asserted. "It's not worth itnot yet."
SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. Light-based therapies are heavily promoted as options for treating acne, but issues of cost and convenience should rule them out as a first line of treatment, said dermatologists at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation. The market is filling up with dozens of different lasers claiming to help treat acne with wide-ranging treatment mechanisms and even wider-ranging price tags, said Jerome Garden, M.D., of the department of dermatology at Northwestern University in Chicago.
"I found 26 different products out there all claiming they treat acne, and it's very hard to sort all of these out," he said.
Most of the claims are backed by some researchinfrared laser treatment, for instance, has some strong studies showing shrinkage of the sebaceous glands; blue light and photodynamic therapy (PDT) are gaining recognition for their efficacy; and radiofrequency devices have shown some success.
But for all of the devices and claims, several confounding factors give dermatologists pause in embracing light-based therapies as a first-line treatment.
First, there is broad inconsistency in the literature. An analysis of acne literature published in the Journal of the American Academy of Dermatology in 2002 underscored the wide-ranging measures used in determining not only outcomes but the very definitions of acne, said James Spencer, M.D., a clinical professor of dermatology at Mount Sinai School of Medicine, New York (J. Am. Acad. Dermatol. 2002;47:23140).
"There were over 25 methods for assessing acne severity and 19 methods for counting lesions," he said. "That makes comparing one study to another very difficult."
With a treatment like PDT, the evidence of efficacy in treating acne is strong, but there is the trade-off of the process being a negative experience for the patient.
"Photochemicals [used in PDT] cause cell membrane damage, and with the process there's pain. The outcome may be positive, but this is not a positive event in the life of the patient," Dr. Garden said.
When PDT is used to treat something like cancerous lesions, the process is entirely justified, but as a repetitive treatment for acne, it is far more questionable, he said.
"What we have to ask ourselves is thisdo we really want this for our patients? And what's the long-term effect? We don't know," he said. "The approach is new, and at the moment I'm very uncomfortable with this."
And then there is the cost of light-based therapies, which are far more expensive than a medical option. "These are highly expensive cash procedures requiring multiple visits to the office," Dr. Spencer said. "I think light-based therapy for acne represents one more tool in the tool chest, but it's quite unreasonable for it to be the first thing that pops into your head."
Dr. Garden agreed. "It's tempting to have a nonmedical option for treating acne, and this may have a role for those very selective, noncompliant patients," he said.
"But when you look at this and ask if it's something that should be a first-line treatment for patients, the answer should be, unequivocally, no," he asserted. "It's not worth itnot yet."
SDEF and this newspaper are wholly owned subsidiaries of Elsevier.