The gene BIRC5 is an “important player” in chondrosarcoma survival, say researchers from Leiden University, The Netherlands, and Athens University, Greece. They propose that targeting survivin, a protein encoded by BIRC5, could lead to a potential avenue for treating the tumor that accounts for 20% of all malignant bone cancers.

Chondrosarcomas are “intrinsically resistant” to chemo- and radiotherapy,” the researchers say, leaving surgery as the only curative option. So they aimed to identify genes that could be used in targeted drug treatment.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

They screened for 51 apoptosis-related genes. When the screening pinpointed survivin as essential for chondrosarcoma survival, the researchers used immunohistochemistry to analyze cytoplasmic survivin expression in 207 chondrosarcomas of different subtypes. Survivin is highly expressed, they found, in tumor tissue and cell lines of conventional as well as rare subtypes of chondrosarcoma.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

The researchers also tested sensitivity to YM155 (a survivin-inhibiting compound) and found chondrosarcoma cells lines were highly sensitive. They say their findings suggest that YM155, which is already in phase I and II clinical trials for other tumors, could be readily applicable in clinical trials for chondrosarcoma patients. Although some larger phase II studies have not shown promising antitumor activity in diffuse large B-cell lymphoma, non-small cell lung cancer, melanoma, or prostate cancer, that doesn’t mean YM155 can’t help in chondrosarcoma patients, they say. Especially, they note, because in chondrosarcoma,YM155 does not induce apoptosis but blocks the cell cycle.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

In particular TP53 mutant cell lines were sensitive; thus, TP53 mutation may be a biomarker that can allow preselecting patients for treatment.

Source:
de Jong Y, van Oosterwijk JG, Kruisselbrink AB. Targeting survivin as a potential new treatment for chondrosarcoma of bone. Oncogenesis. 2016;5:e222.
doi: 10.1038/oncsis.2016.33.

The gene BIRC5 is an “important player” in chondrosarcoma survival, say researchers from Leiden University, The Netherlands, and Athens University, Greece. They propose that targeting survivin, a protein encoded by BIRC5, could lead to a potential avenue for treating the tumor that accounts for 20% of all malignant bone cancers.

Chondrosarcomas are “intrinsically resistant” to chemo- and radiotherapy,” the researchers say, leaving surgery as the only curative option. So they aimed to identify genes that could be used in targeted drug treatment.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

They screened for 51 apoptosis-related genes. When the screening pinpointed survivin as essential for chondrosarcoma survival, the researchers used immunohistochemistry to analyze cytoplasmic survivin expression in 207 chondrosarcomas of different subtypes. Survivin is highly expressed, they found, in tumor tissue and cell lines of conventional as well as rare subtypes of chondrosarcoma.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

The researchers also tested sensitivity to YM155 (a survivin-inhibiting compound) and found chondrosarcoma cells lines were highly sensitive. They say their findings suggest that YM155, which is already in phase I and II clinical trials for other tumors, could be readily applicable in clinical trials for chondrosarcoma patients. Although some larger phase II studies have not shown promising antitumor activity in diffuse large B-cell lymphoma, non-small cell lung cancer, melanoma, or prostate cancer, that doesn’t mean YM155 can’t help in chondrosarcoma patients, they say. Especially, they note, because in chondrosarcoma,YM155 does not induce apoptosis but blocks the cell cycle.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

In particular TP53 mutant cell lines were sensitive; thus, TP53 mutation may be a biomarker that can allow preselecting patients for treatment.

Source:
de Jong Y, van Oosterwijk JG, Kruisselbrink AB. Targeting survivin as a potential new treatment for chondrosarcoma of bone. Oncogenesis. 2016;5:e222.
doi: 10.1038/oncsis.2016.33.

The gene BIRC5 is an “important player” in chondrosarcoma survival, say researchers from Leiden University, The Netherlands, and Athens University, Greece. They propose that targeting survivin, a protein encoded by BIRC5, could lead to a potential avenue for treating the tumor that accounts for 20% of all malignant bone cancers.

Chondrosarcomas are “intrinsically resistant” to chemo- and radiotherapy,” the researchers say, leaving surgery as the only curative option. So they aimed to identify genes that could be used in targeted drug treatment.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

They screened for 51 apoptosis-related genes. When the screening pinpointed survivin as essential for chondrosarcoma survival, the researchers used immunohistochemistry to analyze cytoplasmic survivin expression in 207 chondrosarcomas of different subtypes. Survivin is highly expressed, they found, in tumor tissue and cell lines of conventional as well as rare subtypes of chondrosarcoma.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

The researchers also tested sensitivity to YM155 (a survivin-inhibiting compound) and found chondrosarcoma cells lines were highly sensitive. They say their findings suggest that YM155, which is already in phase I and II clinical trials for other tumors, could be readily applicable in clinical trials for chondrosarcoma patients. Although some larger phase II studies have not shown promising antitumor activity in diffuse large B-cell lymphoma, non-small cell lung cancer, melanoma, or prostate cancer, that doesn’t mean YM155 can’t help in chondrosarcoma patients, they say. Especially, they note, because in chondrosarcoma,YM155 does not induce apoptosis but blocks the cell cycle.

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

In particular TP53 mutant cell lines were sensitive; thus, TP53 mutation may be a biomarker that can allow preselecting patients for treatment.

Source:
de Jong Y, van Oosterwijk JG, Kruisselbrink AB. Targeting survivin as a potential new treatment for chondrosarcoma of bone. Oncogenesis. 2016;5:e222.
doi: 10.1038/oncsis.2016.33.

SAN DIEGO – Statin therapy was independently associated with a substantial survival benefit in women with ovarian cancer in an analysis of the linked Surveillance, Epidemiology and End Results and Medicare databases.

“This is the largest series ever reported supporting the anticancer effect of statin therapy on epithelial ovarian cancer with a concomitant improvement in overall survival. A prospective study in ovarian cancer patients is warranted. Identification of biomarkers that may predict response to statins would help further select patient populations and guide therapy,” Dr. Tilley Jenkins Vogel said in presenting the study results at the annual meeting of the Society of Gynecologic Oncology.

Bruce Jancin/Frontline Medical News

She and her coinvestigators at Cedars-Sinai Medical Center in Los Angeles identified 1,510 women in the SEER registry who were diagnosed with epithelial ovarian cancer during 2007-2009, underwent primary surgical resection, and survived for at least 60 days post surgery. Forty-nine percent were stage III, 25% stage IV. Forty-two percent of the women were on a statin.

Mean overall survival in the statin users was 32.2 months compared to 28.7 months in nonusers. In the stage III cohort, mean overall survival in statin users versus nonusers was 31.7 and 25.9 months.

In a multivariate analysis adjusted for potential confounders of age, race, heart disease and other comorbid conditions prior to cancer diagnosis, and the use of platinum-based chemotherapy, statin therapy was independently associated with a 34% reduction in the risk of mortality. In women whose ovarian cancer histology was serous, statin use was associated with a 31% reduction in death; in those with a nonserous histology, it was a 48% reduction, Dr. Vogel continued.

Diving deeper into the dataset, she found that the overall survival benefit was present only in the 89% of statin users who were on lipophilic statins, such as atorvastatin or simvastatin. This is consistent with other investigators’ reports that the noncardiovascular benefits of statin therapy are largely restricted to the lipophilic class of the LDL-lowering agents.

An anti–ovarian cancer benefit for statin therapy appears to have biologic plausibility, according to Dr. Vogel. She and her coworkers have previously shown synergistic cytotoxicity in vitro when statins are administered concurrently with platinum chemotherapy.

“This effect is believed to be mediated by greater inhibition of cell proliferation, increased apoptosis, and modification of proteins in the RAS pathway,” she said.

Rapidly growing cells, such as cancer cells, require cholesterol to synthesize cell membrane. It’s hypothesized that one mechanism for statins’ anticancer effect is that by reducing intracellular cholesterol levels the drugs interfere with this process, Dr. Vogel noted.

She reported having no financial conflicts regarding this study, conducted without commercial support.

[email protected]

SAN DIEGO – Statin therapy was independently associated with a substantial survival benefit in women with ovarian cancer in an analysis of the linked Surveillance, Epidemiology and End Results and Medicare databases.

“This is the largest series ever reported supporting the anticancer effect of statin therapy on epithelial ovarian cancer with a concomitant improvement in overall survival. A prospective study in ovarian cancer patients is warranted. Identification of biomarkers that may predict response to statins would help further select patient populations and guide therapy,” Dr. Tilley Jenkins Vogel said in presenting the study results at the annual meeting of the Society of Gynecologic Oncology.

Bruce Jancin/Frontline Medical News

She and her coinvestigators at Cedars-Sinai Medical Center in Los Angeles identified 1,510 women in the SEER registry who were diagnosed with epithelial ovarian cancer during 2007-2009, underwent primary surgical resection, and survived for at least 60 days post surgery. Forty-nine percent were stage III, 25% stage IV. Forty-two percent of the women were on a statin.

Mean overall survival in the statin users was 32.2 months compared to 28.7 months in nonusers. In the stage III cohort, mean overall survival in statin users versus nonusers was 31.7 and 25.9 months.

In a multivariate analysis adjusted for potential confounders of age, race, heart disease and other comorbid conditions prior to cancer diagnosis, and the use of platinum-based chemotherapy, statin therapy was independently associated with a 34% reduction in the risk of mortality. In women whose ovarian cancer histology was serous, statin use was associated with a 31% reduction in death; in those with a nonserous histology, it was a 48% reduction, Dr. Vogel continued.

Diving deeper into the dataset, she found that the overall survival benefit was present only in the 89% of statin users who were on lipophilic statins, such as atorvastatin or simvastatin. This is consistent with other investigators’ reports that the noncardiovascular benefits of statin therapy are largely restricted to the lipophilic class of the LDL-lowering agents.

An anti–ovarian cancer benefit for statin therapy appears to have biologic plausibility, according to Dr. Vogel. She and her coworkers have previously shown synergistic cytotoxicity in vitro when statins are administered concurrently with platinum chemotherapy.

“This effect is believed to be mediated by greater inhibition of cell proliferation, increased apoptosis, and modification of proteins in the RAS pathway,” she said.

Rapidly growing cells, such as cancer cells, require cholesterol to synthesize cell membrane. It’s hypothesized that one mechanism for statins’ anticancer effect is that by reducing intracellular cholesterol levels the drugs interfere with this process, Dr. Vogel noted.

She reported having no financial conflicts regarding this study, conducted without commercial support.

[email protected]

SAN DIEGO – Statin therapy was independently associated with a substantial survival benefit in women with ovarian cancer in an analysis of the linked Surveillance, Epidemiology and End Results and Medicare databases.

“This is the largest series ever reported supporting the anticancer effect of statin therapy on epithelial ovarian cancer with a concomitant improvement in overall survival. A prospective study in ovarian cancer patients is warranted. Identification of biomarkers that may predict response to statins would help further select patient populations and guide therapy,” Dr. Tilley Jenkins Vogel said in presenting the study results at the annual meeting of the Society of Gynecologic Oncology.

Bruce Jancin/Frontline Medical News

She and her coinvestigators at Cedars-Sinai Medical Center in Los Angeles identified 1,510 women in the SEER registry who were diagnosed with epithelial ovarian cancer during 2007-2009, underwent primary surgical resection, and survived for at least 60 days post surgery. Forty-nine percent were stage III, 25% stage IV. Forty-two percent of the women were on a statin.

Mean overall survival in the statin users was 32.2 months compared to 28.7 months in nonusers. In the stage III cohort, mean overall survival in statin users versus nonusers was 31.7 and 25.9 months.

In a multivariate analysis adjusted for potential confounders of age, race, heart disease and other comorbid conditions prior to cancer diagnosis, and the use of platinum-based chemotherapy, statin therapy was independently associated with a 34% reduction in the risk of mortality. In women whose ovarian cancer histology was serous, statin use was associated with a 31% reduction in death; in those with a nonserous histology, it was a 48% reduction, Dr. Vogel continued.

Diving deeper into the dataset, she found that the overall survival benefit was present only in the 89% of statin users who were on lipophilic statins, such as atorvastatin or simvastatin. This is consistent with other investigators’ reports that the noncardiovascular benefits of statin therapy are largely restricted to the lipophilic class of the LDL-lowering agents.

An anti–ovarian cancer benefit for statin therapy appears to have biologic plausibility, according to Dr. Vogel. She and her coworkers have previously shown synergistic cytotoxicity in vitro when statins are administered concurrently with platinum chemotherapy.

“This effect is believed to be mediated by greater inhibition of cell proliferation, increased apoptosis, and modification of proteins in the RAS pathway,” she said.

Rapidly growing cells, such as cancer cells, require cholesterol to synthesize cell membrane. It’s hypothesized that one mechanism for statins’ anticancer effect is that by reducing intracellular cholesterol levels the drugs interfere with this process, Dr. Vogel noted.

She reported having no financial conflicts regarding this study, conducted without commercial support.

[email protected]

Chicago – A newly developed heat shock protein peptide vaccination appears to be safe and effective in treating patients with newly diagnosed glioblastoma (GBM), according to the results of a phase II single arm study.

In adding the vaccine to standard therapy for 46 patients with newly diagnosed GBM, median overall survival was 23.8 months, and there were no grade 3 or 4 adverse events associated with the vaccine, lead author Dr. Orin Bloch of Northwestern University, Chicago, reported at the annual meeting of the American Society of Clinical Oncology.

Standard therapy typically results in a median survival of 16 months, he said.

“There is a lot of information out there right now regarding CNS and other solid organ tumors particularly in the area of checkpoint modulation and its ability to stimulate an innate immune response against a tumor. I think in GBM we are facing a bit of a different scenario, however, because the tumor exists in a very privileged area behind the blood brain barrier and doesn’t regularly metastasize beyond the CNS,” Dr. Bloch said.

Therefore, only modulating checkpoints without stimulating and educating the immune system may not be the most effective approach. Adaptive immunity through vaccination or some other form of stimulation might be more successful, Dr. Bloch said.

“As a way of inducing immune stimulation and education using tumor-autologous peptides, one can capitalize on the native system of heat shock stimulation. Heat shock proteins are chaperone proteins that are ubiquitously expressed in cells and they’re bound to any number of intracellular peptides at any one time including, in tumor cells, neoantigens. If you extract these heat shock proteins with their bound antigens and deliver them in a naked form into the systemic circulation, their uptake into antigen-presenting cells through the CD91 receptor [will result in] the peptide [being] cleaved and presented on MHC class one and two for stimulation of CD8- and CD4-positive T cell response,” he said.

Heat shock proteins also interact with toll-like receptors and stimulate the secretion of pro-inflammatory cytokines, “acting as their own adjuvant,” Dr. Bloch further explained. Utilizing heat shock proteins activates both the innate and adaptive immune responses.

“This is an ideal platform for developing an immunotherapy for glioblastoma,” Dr. Bloch said.

In this phase II study, 46 adult patients with GBM underwent surgical resection of their tumors followed by chemoradiotherapy. At least four 25-microgram doses of vaccine were generated from tissue obtained during surgery. Within 5 weeks of completing radiotherapy, patients began receiving weekly vaccinations in combination with adjuvant temozolomide. Patients continued receiving vaccines until depletion or until tumor progression.

Median progression-free survival was 17.8 months (95% confidence interval, 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2).

PD-L1 expression on circulating monocytes was also measured from peripheral blood samples obtained during surgery. Patients were classified as having either high PD-L1 expression (54.5% or more of monocytes) or low PD-L1 expression. Among patients classified as having high PD-L1 expression, the median overall survival was 18.0 months (95% CI, 10.0-23.3). Patients who had low PD-L1 expression had a significantly longer median overall survival time of 44.7 months with a confidence interval not calculable (hazard ratio, 3.35; 95% CI, 1.36-8.23; P = .003).

Finally, a multivariate proportional hazards model showed the MGMT methylation status and PD-L1 expression were the two greatest independent predictors of survival.

“Survival among patients who received the HSPPV-96 was greater than expected compared to historical controls... These results certainly, we feel, provide rationale for a phase III trial of vaccine plus standard of care versus standard of care alone,” Dr. Bloch said.

“PD-L1 expression on circulating myeloid cells is independently predictive of clinical response to vaccination, and it suggests that the low PD-L1 expressing population will most benefit from this anti-tumor vaccination scheme, but it also suggests that high PD-L1 expressing patients may benefit from combined checkpoint inhibition. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy,” Dr. Bloch further commented.

This study was funded by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, the National Brain Tumor Society, the American Brain Tumor Association, and Accelerated Brain Cancer Cure. Dr. Bloch reporting having no relevant disclosures.

[email protected]

On Twitter @jessnicolecraig

Chicago – A newly developed heat shock protein peptide vaccination appears to be safe and effective in treating patients with newly diagnosed glioblastoma (GBM), according to the results of a phase II single arm study.

In adding the vaccine to standard therapy for 46 patients with newly diagnosed GBM, median overall survival was 23.8 months, and there were no grade 3 or 4 adverse events associated with the vaccine, lead author Dr. Orin Bloch of Northwestern University, Chicago, reported at the annual meeting of the American Society of Clinical Oncology.

Standard therapy typically results in a median survival of 16 months, he said.

“There is a lot of information out there right now regarding CNS and other solid organ tumors particularly in the area of checkpoint modulation and its ability to stimulate an innate immune response against a tumor. I think in GBM we are facing a bit of a different scenario, however, because the tumor exists in a very privileged area behind the blood brain barrier and doesn’t regularly metastasize beyond the CNS,” Dr. Bloch said.

Therefore, only modulating checkpoints without stimulating and educating the immune system may not be the most effective approach. Adaptive immunity through vaccination or some other form of stimulation might be more successful, Dr. Bloch said.

“As a way of inducing immune stimulation and education using tumor-autologous peptides, one can capitalize on the native system of heat shock stimulation. Heat shock proteins are chaperone proteins that are ubiquitously expressed in cells and they’re bound to any number of intracellular peptides at any one time including, in tumor cells, neoantigens. If you extract these heat shock proteins with their bound antigens and deliver them in a naked form into the systemic circulation, their uptake into antigen-presenting cells through the CD91 receptor [will result in] the peptide [being] cleaved and presented on MHC class one and two for stimulation of CD8- and CD4-positive T cell response,” he said.

Heat shock proteins also interact with toll-like receptors and stimulate the secretion of pro-inflammatory cytokines, “acting as their own adjuvant,” Dr. Bloch further explained. Utilizing heat shock proteins activates both the innate and adaptive immune responses.

“This is an ideal platform for developing an immunotherapy for glioblastoma,” Dr. Bloch said.

In this phase II study, 46 adult patients with GBM underwent surgical resection of their tumors followed by chemoradiotherapy. At least four 25-microgram doses of vaccine were generated from tissue obtained during surgery. Within 5 weeks of completing radiotherapy, patients began receiving weekly vaccinations in combination with adjuvant temozolomide. Patients continued receiving vaccines until depletion or until tumor progression.

Median progression-free survival was 17.8 months (95% confidence interval, 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2).

PD-L1 expression on circulating monocytes was also measured from peripheral blood samples obtained during surgery. Patients were classified as having either high PD-L1 expression (54.5% or more of monocytes) or low PD-L1 expression. Among patients classified as having high PD-L1 expression, the median overall survival was 18.0 months (95% CI, 10.0-23.3). Patients who had low PD-L1 expression had a significantly longer median overall survival time of 44.7 months with a confidence interval not calculable (hazard ratio, 3.35; 95% CI, 1.36-8.23; P = .003).

Finally, a multivariate proportional hazards model showed the MGMT methylation status and PD-L1 expression were the two greatest independent predictors of survival.

“Survival among patients who received the HSPPV-96 was greater than expected compared to historical controls... These results certainly, we feel, provide rationale for a phase III trial of vaccine plus standard of care versus standard of care alone,” Dr. Bloch said.

“PD-L1 expression on circulating myeloid cells is independently predictive of clinical response to vaccination, and it suggests that the low PD-L1 expressing population will most benefit from this anti-tumor vaccination scheme, but it also suggests that high PD-L1 expressing patients may benefit from combined checkpoint inhibition. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy,” Dr. Bloch further commented.

This study was funded by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, the National Brain Tumor Society, the American Brain Tumor Association, and Accelerated Brain Cancer Cure. Dr. Bloch reporting having no relevant disclosures.

[email protected]

On Twitter @jessnicolecraig

Chicago – A newly developed heat shock protein peptide vaccination appears to be safe and effective in treating patients with newly diagnosed glioblastoma (GBM), according to the results of a phase II single arm study.

In adding the vaccine to standard therapy for 46 patients with newly diagnosed GBM, median overall survival was 23.8 months, and there were no grade 3 or 4 adverse events associated with the vaccine, lead author Dr. Orin Bloch of Northwestern University, Chicago, reported at the annual meeting of the American Society of Clinical Oncology.

Standard therapy typically results in a median survival of 16 months, he said.

“There is a lot of information out there right now regarding CNS and other solid organ tumors particularly in the area of checkpoint modulation and its ability to stimulate an innate immune response against a tumor. I think in GBM we are facing a bit of a different scenario, however, because the tumor exists in a very privileged area behind the blood brain barrier and doesn’t regularly metastasize beyond the CNS,” Dr. Bloch said.

Therefore, only modulating checkpoints without stimulating and educating the immune system may not be the most effective approach. Adaptive immunity through vaccination or some other form of stimulation might be more successful, Dr. Bloch said.

“As a way of inducing immune stimulation and education using tumor-autologous peptides, one can capitalize on the native system of heat shock stimulation. Heat shock proteins are chaperone proteins that are ubiquitously expressed in cells and they’re bound to any number of intracellular peptides at any one time including, in tumor cells, neoantigens. If you extract these heat shock proteins with their bound antigens and deliver them in a naked form into the systemic circulation, their uptake into antigen-presenting cells through the CD91 receptor [will result in] the peptide [being] cleaved and presented on MHC class one and two for stimulation of CD8- and CD4-positive T cell response,” he said.

Heat shock proteins also interact with toll-like receptors and stimulate the secretion of pro-inflammatory cytokines, “acting as their own adjuvant,” Dr. Bloch further explained. Utilizing heat shock proteins activates both the innate and adaptive immune responses.

“This is an ideal platform for developing an immunotherapy for glioblastoma,” Dr. Bloch said.

In this phase II study, 46 adult patients with GBM underwent surgical resection of their tumors followed by chemoradiotherapy. At least four 25-microgram doses of vaccine were generated from tissue obtained during surgery. Within 5 weeks of completing radiotherapy, patients began receiving weekly vaccinations in combination with adjuvant temozolomide. Patients continued receiving vaccines until depletion or until tumor progression.

Median progression-free survival was 17.8 months (95% confidence interval, 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2).

PD-L1 expression on circulating monocytes was also measured from peripheral blood samples obtained during surgery. Patients were classified as having either high PD-L1 expression (54.5% or more of monocytes) or low PD-L1 expression. Among patients classified as having high PD-L1 expression, the median overall survival was 18.0 months (95% CI, 10.0-23.3). Patients who had low PD-L1 expression had a significantly longer median overall survival time of 44.7 months with a confidence interval not calculable (hazard ratio, 3.35; 95% CI, 1.36-8.23; P = .003).

Finally, a multivariate proportional hazards model showed the MGMT methylation status and PD-L1 expression were the two greatest independent predictors of survival.

“Survival among patients who received the HSPPV-96 was greater than expected compared to historical controls... These results certainly, we feel, provide rationale for a phase III trial of vaccine plus standard of care versus standard of care alone,” Dr. Bloch said.

“PD-L1 expression on circulating myeloid cells is independently predictive of clinical response to vaccination, and it suggests that the low PD-L1 expressing population will most benefit from this anti-tumor vaccination scheme, but it also suggests that high PD-L1 expressing patients may benefit from combined checkpoint inhibition. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy,” Dr. Bloch further commented.

This study was funded by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, the National Brain Tumor Society, the American Brain Tumor Association, and Accelerated Brain Cancer Cure. Dr. Bloch reporting having no relevant disclosures.

[email protected]

On Twitter @jessnicolecraig

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

View a chart outlining key communication tactics

What I Say and Do

I use the teach-back method to confirm my patients’ understanding.

Why I Do It

Teach-back allows me to address my patients’ uncertainty about the plan and clarify any misunderstandings.

As doctors, one of our most important jobs is explaining in ways our patients understand. It doesn’t matter how brilliant our treatment plan is if our patients do not understand it. We all want to feel like we’re making a difference in our patients’ lives. Yet it’s hard for our patients to do what we recommend if they don’t understand.

Unfortunately, many patients are too embarrassed to ask questions, or they simply do not know what to ask. Patients will also say they understand everything even when they do not because they fear appearing uneducated.

This is why the teach-back method is so valuable. The teach-back method allows you to better assess your patients’ understanding of their medical problems. It allows you to uncover and clarify any misunderstandings your patients may have about the plan. It also helps you to engage in a more collaborative relationship with your patients.

How I Do It

Teach-back helps me to test my effectiveness as a teacher by allowing me to assess whether my patient understands; if not, I explain in a different way.

One of the common mistakes clinicians make when assessing for understanding is asking, “Do you have any questions?” or “Does this make sense?” The problem with these questions is that they are closed-ended. The only responses are yes or no. Your patients may say they understand even when they do not. In reality, it does not matter how brilliant your treatment plans are if patients do not follow them because they do not understand.

Teach-back encourages the doctor to check for understanding by using open-ended instead of closed-ended questions.

Example one: “This is a new diagnosis for you, so I want to make sure you understand. Will you tell me in your own words what congestive heart failure is?”

Example two: “I want to make sure I explained this clearly. I know your daughter helps you manage your health. What will you tell her about the changes we made to your blood pressure medication?”

Teach-back steps:

1. I explain the concept to my patients, avoiding medical jargon.
2. I assess my patients’ understanding by asking them to explain the concept in their own words.
3. I clarify anything my patients did not understand and reassess their understanding.
4. If my patients still do not understand, I find a new way to explain the concept.
5. I repeat the process of explaining and assessing for understanding until my patients are able to accurately state their understanding.

There are a few key things to remember as you perform teach-back. The first is to ensure you use a caring tone when speaking with your patients. Next, if you have several concepts you want to teach, break it into small pieces. Use teach-back for the first concept before moving on to the next. Finally, one of the most common questions I get from other doctors about teach-back is how to assess patients’ understanding without sounding condescending. I address this by making it about me and my effectiveness as a teacher. I tell my patients it is my responsibility to explain things in a way they understand, so if they do not, I will explain it in a different way. When I frame it this way, patients are not offended by my asking them to perform teach-back because they realize I’m doing it as a test of my effectiveness as a teacher.

Example: “Mr. Johnson, as your doctor, one of my top priorities is to ensure I’m explaining things in a way you understand. I want to make sure my instructions about how to take your new medication are clear. Would you mind telling me in your own words how you will take this new medication?”

Now that you know what teach-back is and understand how helpful it can be, start incorporating it into your practice. Think about a few concepts that you teach again and again, such as disease management, medication changes, and self-care instructions. Next, think about how you could use teach-back in these scenarios. Practice what you will say when you ask patients to engage in teach-back. Finally, commit to using teach-back with your next few patients. The more you practice, the easier it becomes.

For more information on teach-back, visit www.teachbacktraining.org.

Dr. Dorrah is regional medical director for quality and the patient experience, Baylor Scott & White Health, Round Rock, Texas.

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

View a chart outlining key communication tactics

What I Say and Do

I use the teach-back method to confirm my patients’ understanding.

Why I Do It

Teach-back allows me to address my patients’ uncertainty about the plan and clarify any misunderstandings.

As doctors, one of our most important jobs is explaining in ways our patients understand. It doesn’t matter how brilliant our treatment plan is if our patients do not understand it. We all want to feel like we’re making a difference in our patients’ lives. Yet it’s hard for our patients to do what we recommend if they don’t understand.

Unfortunately, many patients are too embarrassed to ask questions, or they simply do not know what to ask. Patients will also say they understand everything even when they do not because they fear appearing uneducated.

This is why the teach-back method is so valuable. The teach-back method allows you to better assess your patients’ understanding of their medical problems. It allows you to uncover and clarify any misunderstandings your patients may have about the plan. It also helps you to engage in a more collaborative relationship with your patients.

How I Do It

Teach-back helps me to test my effectiveness as a teacher by allowing me to assess whether my patient understands; if not, I explain in a different way.

One of the common mistakes clinicians make when assessing for understanding is asking, “Do you have any questions?” or “Does this make sense?” The problem with these questions is that they are closed-ended. The only responses are yes or no. Your patients may say they understand even when they do not. In reality, it does not matter how brilliant your treatment plans are if patients do not follow them because they do not understand.

Teach-back encourages the doctor to check for understanding by using open-ended instead of closed-ended questions.

Example one: “This is a new diagnosis for you, so I want to make sure you understand. Will you tell me in your own words what congestive heart failure is?”

Example two: “I want to make sure I explained this clearly. I know your daughter helps you manage your health. What will you tell her about the changes we made to your blood pressure medication?”

Teach-back steps:

1. I explain the concept to my patients, avoiding medical jargon.
2. I assess my patients’ understanding by asking them to explain the concept in their own words.
3. I clarify anything my patients did not understand and reassess their understanding.
4. If my patients still do not understand, I find a new way to explain the concept.
5. I repeat the process of explaining and assessing for understanding until my patients are able to accurately state their understanding.

There are a few key things to remember as you perform teach-back. The first is to ensure you use a caring tone when speaking with your patients. Next, if you have several concepts you want to teach, break it into small pieces. Use teach-back for the first concept before moving on to the next. Finally, one of the most common questions I get from other doctors about teach-back is how to assess patients’ understanding without sounding condescending. I address this by making it about me and my effectiveness as a teacher. I tell my patients it is my responsibility to explain things in a way they understand, so if they do not, I will explain it in a different way. When I frame it this way, patients are not offended by my asking them to perform teach-back because they realize I’m doing it as a test of my effectiveness as a teacher.

Example: “Mr. Johnson, as your doctor, one of my top priorities is to ensure I’m explaining things in a way you understand. I want to make sure my instructions about how to take your new medication are clear. Would you mind telling me in your own words how you will take this new medication?”

Now that you know what teach-back is and understand how helpful it can be, start incorporating it into your practice. Think about a few concepts that you teach again and again, such as disease management, medication changes, and self-care instructions. Next, think about how you could use teach-back in these scenarios. Practice what you will say when you ask patients to engage in teach-back. Finally, commit to using teach-back with your next few patients. The more you practice, the easier it becomes.

For more information on teach-back, visit www.teachbacktraining.org.

Dr. Dorrah is regional medical director for quality and the patient experience, Baylor Scott & White Health, Round Rock, Texas.

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

View a chart outlining key communication tactics

What I Say and Do

I use the teach-back method to confirm my patients’ understanding.

Why I Do It

Teach-back allows me to address my patients’ uncertainty about the plan and clarify any misunderstandings.

As doctors, one of our most important jobs is explaining in ways our patients understand. It doesn’t matter how brilliant our treatment plan is if our patients do not understand it. We all want to feel like we’re making a difference in our patients’ lives. Yet it’s hard for our patients to do what we recommend if they don’t understand.

Unfortunately, many patients are too embarrassed to ask questions, or they simply do not know what to ask. Patients will also say they understand everything even when they do not because they fear appearing uneducated.

This is why the teach-back method is so valuable. The teach-back method allows you to better assess your patients’ understanding of their medical problems. It allows you to uncover and clarify any misunderstandings your patients may have about the plan. It also helps you to engage in a more collaborative relationship with your patients.

How I Do It

Teach-back helps me to test my effectiveness as a teacher by allowing me to assess whether my patient understands; if not, I explain in a different way.

One of the common mistakes clinicians make when assessing for understanding is asking, “Do you have any questions?” or “Does this make sense?” The problem with these questions is that they are closed-ended. The only responses are yes or no. Your patients may say they understand even when they do not. In reality, it does not matter how brilliant your treatment plans are if patients do not follow them because they do not understand.

Teach-back encourages the doctor to check for understanding by using open-ended instead of closed-ended questions.

Example one: “This is a new diagnosis for you, so I want to make sure you understand. Will you tell me in your own words what congestive heart failure is?”

Example two: “I want to make sure I explained this clearly. I know your daughter helps you manage your health. What will you tell her about the changes we made to your blood pressure medication?”

Teach-back steps:

1. I explain the concept to my patients, avoiding medical jargon.
2. I assess my patients’ understanding by asking them to explain the concept in their own words.
3. I clarify anything my patients did not understand and reassess their understanding.
4. If my patients still do not understand, I find a new way to explain the concept.
5. I repeat the process of explaining and assessing for understanding until my patients are able to accurately state their understanding.

There are a few key things to remember as you perform teach-back. The first is to ensure you use a caring tone when speaking with your patients. Next, if you have several concepts you want to teach, break it into small pieces. Use teach-back for the first concept before moving on to the next. Finally, one of the most common questions I get from other doctors about teach-back is how to assess patients’ understanding without sounding condescending. I address this by making it about me and my effectiveness as a teacher. I tell my patients it is my responsibility to explain things in a way they understand, so if they do not, I will explain it in a different way. When I frame it this way, patients are not offended by my asking them to perform teach-back because they realize I’m doing it as a test of my effectiveness as a teacher.

Example: “Mr. Johnson, as your doctor, one of my top priorities is to ensure I’m explaining things in a way you understand. I want to make sure my instructions about how to take your new medication are clear. Would you mind telling me in your own words how you will take this new medication?”

Now that you know what teach-back is and understand how helpful it can be, start incorporating it into your practice. Think about a few concepts that you teach again and again, such as disease management, medication changes, and self-care instructions. Next, think about how you could use teach-back in these scenarios. Practice what you will say when you ask patients to engage in teach-back. Finally, commit to using teach-back with your next few patients. The more you practice, the easier it becomes.

For more information on teach-back, visit www.teachbacktraining.org.

Dr. Dorrah is regional medical director for quality and the patient experience, Baylor Scott & White Health, Round Rock, Texas.

 

 

Max S. Topp, MD

 

COPENHAGEN—Interim results from the phase 3 TOWER trial suggest blinatumomab can prolong overall survival (OS) when compared to standard care in adults with Ph-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

The median OS for patients treated with blinatumomab was nearly double the median OS of patients who received standard chemotherapy (investigator’s choice of 4 different regimens).

Based on these results, Amgen, the company sponsoring the trial, decided to stop it early.

“This was the first study to show that immunotherapy can outcompete chemotherapy,” said Max S. Topp, MD, of University Hospital of Wuerzburg in Germany.

Dr Topp presented results from this study at the 21st Congress of the European Hematology Association (abstract S149).

Patients and treatment

The TOWER trial enrolled and randomized 405 patients with Ph-negative, relapsed/refractory B-ALL, and 376 of them ultimately received treatment.

The patients received blinatumomab (n=267) or investigator’s choice of 1 of 4 protocol-defined standard chemotherapy regimens (n=109):

• FLAG (fludarabine, high-dose cytarabine, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
• A high-dose cytarabine-based regimen (n=19, 17%)
• A high-dose methotrexate-based regimen (n=22, 20%)
• A clofarabine-based regimen (n=19, 17%).

Patients who received blinatumomab received it as a continuous infusion, 4 weeks on and 2 weeks off, at 9 µg/day for 7 days, then 28 µg/day on weeks 2-4. They received 2 cycles of induction, which was followed by 3 cycles of consolidation if they had ≤5% blasts.

If patients still had ≤5% blasts after consolidation, they received up to 12 months of blinatumomab maintenance. Maintenance was a continuous infusion, 4 weeks on and 8 weeks off, at 28 µg/day.

Patient characteristics were similar between the treatment arms. The median age was 37 in both arms (overall range, 18-80). About 40% of patients in the blinatumomab arm and 50% in the chemotherapy arm had not received any prior salvage regimens.

More than 30% of patients in both arms had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT), and about 20% were primary refractory. Roughly 30% of blinatumomab-treated patients were refractory to salvage therapy, as were more than 20% of chemotherapy-treated patients.

Response and survival

During induction, in the intent-to-treat population (n=271 in the blinatumomab arm and 134 in the chemotherapy arm), the overall response rate was 44% in the blinatumomab arm and 25% in the chemotherapy arm (P<0.001). The complete response rates were 34% and 16%, respectively.

Among patients who received their assigned treatment (n=267 in the blinatumomab arm and 109 in the chemotherapy arm), the overall response rates were 45% and 30%, respectively (P=0.007).

In the intent-to-treat population, the median OS was 7.7 months (95% CI, 5.6-9.6) in the blinatumomab arm and 4 months (95% CI, 2.9-5.3) in the chemotherapy arm (hazard ratio=0.71, P=0.012). The survival curves were similar in the as-treated population.

Dr Topp noted that the improvement in OS with blinatumomab was consistent across subgroups, regardless of age, prior salvage therapy, or prior allo-HSCT.

Dr Topp and his colleagues also considered the effect post-treatment allo-HSCT might have on OS. Sixty-five patients in the blinatumomab arm and 32 in the chemotherapy arm went on to receive an allo-HSCT (24% of patients in both arms).

When the researchers censored for post-treatment allo-HSCT, the median OS was 6.9 months in the blinatumomab arm and 3.9 months in the chemotherapy arm (hazard ratio=0.66, P=0.004).

Safety

In the as-treated population, 99% of patients in both arms experienced adverse events (AEs).


The incidence of grade 3 AEs was 37% in the blinatumomab arm and 30% in the chemotherapy arm. The incidence of grade 4 AEs was 31% and 44%, respectively. The incidence of grade 5 AEs was 19% and 17%, respectively.

Grade 3 or higher AEs of interest, according to Dr Topp, were infection (34% with blinatumomab and 52% with chemotherapy), neutropenia (38% and 58%, respectively), neurologic events (9% and 8%, respectively), and cytokine release syndrome (5% and 0%, respectively).

Seven patients—5 in the blinatumomab arm and 2 in the chemotherapy arm—who did not undergo allo-HSCT died during the study without documented relapse.

 

 

Max S. Topp, MD

 

COPENHAGEN—Interim results from the phase 3 TOWER trial suggest blinatumomab can prolong overall survival (OS) when compared to standard care in adults with Ph-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

The median OS for patients treated with blinatumomab was nearly double the median OS of patients who received standard chemotherapy (investigator’s choice of 4 different regimens).

Based on these results, Amgen, the company sponsoring the trial, decided to stop it early.

“This was the first study to show that immunotherapy can outcompete chemotherapy,” said Max S. Topp, MD, of University Hospital of Wuerzburg in Germany.

Dr Topp presented results from this study at the 21st Congress of the European Hematology Association (abstract S149).

Patients and treatment

The TOWER trial enrolled and randomized 405 patients with Ph-negative, relapsed/refractory B-ALL, and 376 of them ultimately received treatment.

The patients received blinatumomab (n=267) or investigator’s choice of 1 of 4 protocol-defined standard chemotherapy regimens (n=109):

• FLAG (fludarabine, high-dose cytarabine, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
• A high-dose cytarabine-based regimen (n=19, 17%)
• A high-dose methotrexate-based regimen (n=22, 20%)
• A clofarabine-based regimen (n=19, 17%).

Patients who received blinatumomab received it as a continuous infusion, 4 weeks on and 2 weeks off, at 9 µg/day for 7 days, then 28 µg/day on weeks 2-4. They received 2 cycles of induction, which was followed by 3 cycles of consolidation if they had ≤5% blasts.

If patients still had ≤5% blasts after consolidation, they received up to 12 months of blinatumomab maintenance. Maintenance was a continuous infusion, 4 weeks on and 8 weeks off, at 28 µg/day.

Patient characteristics were similar between the treatment arms. The median age was 37 in both arms (overall range, 18-80). About 40% of patients in the blinatumomab arm and 50% in the chemotherapy arm had not received any prior salvage regimens.

More than 30% of patients in both arms had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT), and about 20% were primary refractory. Roughly 30% of blinatumomab-treated patients were refractory to salvage therapy, as were more than 20% of chemotherapy-treated patients.

Response and survival

During induction, in the intent-to-treat population (n=271 in the blinatumomab arm and 134 in the chemotherapy arm), the overall response rate was 44% in the blinatumomab arm and 25% in the chemotherapy arm (P<0.001). The complete response rates were 34% and 16%, respectively.

Among patients who received their assigned treatment (n=267 in the blinatumomab arm and 109 in the chemotherapy arm), the overall response rates were 45% and 30%, respectively (P=0.007).

In the intent-to-treat population, the median OS was 7.7 months (95% CI, 5.6-9.6) in the blinatumomab arm and 4 months (95% CI, 2.9-5.3) in the chemotherapy arm (hazard ratio=0.71, P=0.012). The survival curves were similar in the as-treated population.

Dr Topp noted that the improvement in OS with blinatumomab was consistent across subgroups, regardless of age, prior salvage therapy, or prior allo-HSCT.

Dr Topp and his colleagues also considered the effect post-treatment allo-HSCT might have on OS. Sixty-five patients in the blinatumomab arm and 32 in the chemotherapy arm went on to receive an allo-HSCT (24% of patients in both arms).

When the researchers censored for post-treatment allo-HSCT, the median OS was 6.9 months in the blinatumomab arm and 3.9 months in the chemotherapy arm (hazard ratio=0.66, P=0.004).

Safety

In the as-treated population, 99% of patients in both arms experienced adverse events (AEs).


The incidence of grade 3 AEs was 37% in the blinatumomab arm and 30% in the chemotherapy arm. The incidence of grade 4 AEs was 31% and 44%, respectively. The incidence of grade 5 AEs was 19% and 17%, respectively.

Grade 3 or higher AEs of interest, according to Dr Topp, were infection (34% with blinatumomab and 52% with chemotherapy), neutropenia (38% and 58%, respectively), neurologic events (9% and 8%, respectively), and cytokine release syndrome (5% and 0%, respectively).

Seven patients—5 in the blinatumomab arm and 2 in the chemotherapy arm—who did not undergo allo-HSCT died during the study without documented relapse.

 

 

Max S. Topp, MD

 

COPENHAGEN—Interim results from the phase 3 TOWER trial suggest blinatumomab can prolong overall survival (OS) when compared to standard care in adults with Ph-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

The median OS for patients treated with blinatumomab was nearly double the median OS of patients who received standard chemotherapy (investigator’s choice of 4 different regimens).

Based on these results, Amgen, the company sponsoring the trial, decided to stop it early.

“This was the first study to show that immunotherapy can outcompete chemotherapy,” said Max S. Topp, MD, of University Hospital of Wuerzburg in Germany.

Dr Topp presented results from this study at the 21st Congress of the European Hematology Association (abstract S149).

Patients and treatment

The TOWER trial enrolled and randomized 405 patients with Ph-negative, relapsed/refractory B-ALL, and 376 of them ultimately received treatment.

The patients received blinatumomab (n=267) or investigator’s choice of 1 of 4 protocol-defined standard chemotherapy regimens (n=109):

• FLAG (fludarabine, high-dose cytarabine, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
• A high-dose cytarabine-based regimen (n=19, 17%)
• A high-dose methotrexate-based regimen (n=22, 20%)
• A clofarabine-based regimen (n=19, 17%).

Patients who received blinatumomab received it as a continuous infusion, 4 weeks on and 2 weeks off, at 9 µg/day for 7 days, then 28 µg/day on weeks 2-4. They received 2 cycles of induction, which was followed by 3 cycles of consolidation if they had ≤5% blasts.

If patients still had ≤5% blasts after consolidation, they received up to 12 months of blinatumomab maintenance. Maintenance was a continuous infusion, 4 weeks on and 8 weeks off, at 28 µg/day.

Patient characteristics were similar between the treatment arms. The median age was 37 in both arms (overall range, 18-80). About 40% of patients in the blinatumomab arm and 50% in the chemotherapy arm had not received any prior salvage regimens.

More than 30% of patients in both arms had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT), and about 20% were primary refractory. Roughly 30% of blinatumomab-treated patients were refractory to salvage therapy, as were more than 20% of chemotherapy-treated patients.

Response and survival

During induction, in the intent-to-treat population (n=271 in the blinatumomab arm and 134 in the chemotherapy arm), the overall response rate was 44% in the blinatumomab arm and 25% in the chemotherapy arm (P<0.001). The complete response rates were 34% and 16%, respectively.

Among patients who received their assigned treatment (n=267 in the blinatumomab arm and 109 in the chemotherapy arm), the overall response rates were 45% and 30%, respectively (P=0.007).

In the intent-to-treat population, the median OS was 7.7 months (95% CI, 5.6-9.6) in the blinatumomab arm and 4 months (95% CI, 2.9-5.3) in the chemotherapy arm (hazard ratio=0.71, P=0.012). The survival curves were similar in the as-treated population.

Dr Topp noted that the improvement in OS with blinatumomab was consistent across subgroups, regardless of age, prior salvage therapy, or prior allo-HSCT.

Dr Topp and his colleagues also considered the effect post-treatment allo-HSCT might have on OS. Sixty-five patients in the blinatumomab arm and 32 in the chemotherapy arm went on to receive an allo-HSCT (24% of patients in both arms).

When the researchers censored for post-treatment allo-HSCT, the median OS was 6.9 months in the blinatumomab arm and 3.9 months in the chemotherapy arm (hazard ratio=0.66, P=0.004).

Safety

In the as-treated population, 99% of patients in both arms experienced adverse events (AEs).


The incidence of grade 3 AEs was 37% in the blinatumomab arm and 30% in the chemotherapy arm. The incidence of grade 4 AEs was 31% and 44%, respectively. The incidence of grade 5 AEs was 19% and 17%, respectively.

Grade 3 or higher AEs of interest, according to Dr Topp, were infection (34% with blinatumomab and 52% with chemotherapy), neutropenia (38% and 58%, respectively), neurologic events (9% and 8%, respectively), and cytokine release syndrome (5% and 0%, respectively).

Seven patients—5 in the blinatumomab arm and 2 in the chemotherapy arm—who did not undergo allo-HSCT died during the study without documented relapse.

Uwe Platzbecker, MD

COPENHAGEN—The erythropoiesis-stimulating agent (ESA) darbepoetin alfa can provide a clinical benefit in patients with lower-risk myelodysplastic syndromes (MDS), a phase 3 trial suggests.

In the ARCADE trial, darbepoetin alfa significantly reduced the incidence of red blood cell (RBC) transfusions in patients with low- and intermediate-1 risk myelodysplastic syndrome (MDS), when compared to placebo.

The ESA also significantly improved erythroid response.

In addition, researchers said adverse events (AEs) were generally balanced between the darbepoetin alfa and placebo arms.

Uwe Platzbecker, MD, of University Hospital Carl Gustav Carus Dresden in Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S128). The ARCADE trial was sponsored by Amgen.

Dr Platzbecker noted that, although ESAs are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, the drugs are not widely approved for this indication.

So, in the ARCADE trial, he and his colleagues assessed darbepoetin alfa in patients with low- or intermediate-1 risk MDS who had not previously taken ESAs or biologic response modifiers.

The patients had hemoglobin levels ≤10 g/dL, endogenous erythropoietin levels ≤500 mU/mL, and low transfusion burden (<4 RBC units in each of 2 consecutive 8-week periods prior to randomization).

During a 24-week period, 147 patients received either darbepoetin alfa at 500 μg (n=97) or placebo (n=49) every 3 weeks. The ESA dose was withheld if patients’ hemoglobin was >12.0 g/dL and decreased if hemoglobin increased by >1.5 g/dL in 3 weeks without transfusion.

At week 25, when the primary and key secondary endpoints were assessed, patients underwent an end-of-treatment period visit. They could then enter a 48-week active treatment period and cross over to receive darbepoetin alfa, with dose escalation allowed beginning on week 31. Treatment continued until week 72 or 73, and patients continue to be assessed every 26 weeks, for a minimum of 3 years.

Patient characteristics

Dr Platzbecker said baseline demographic and disease characteristics were generally similar between the treatment arms. All patients were Caucasian, and about 55% were male. The median age was 74 (range, 67-79). About half of patients in each treatment arm belonged to the low-risk IPSS category.

In both arms, most patients had refractory cytopenia with multilineage dysplasia (38.8% in the placebo arm and 46.4% in the darbepoetin alfa arm). Patients also had refractory anemia with excess blasts-1 (20.4% and 13.4%, respectively), refractory anemia (26.5% and 9.3%), refractory anemia with ring sideroblasts (8.2% and 17.5%), 5q deletion (4.1% and 11.3%), unclassifiable MDS (2.0% and 1.0%), and MDS of an unknown type (0% and 1.0%).

In the 16 weeks before randomization, 58.2% of all patients—53.1% in the placebo arm and 60.8% in the darbepoetin alfa arm—did not have any RBC transfusions. About 25% (24.7%)—22.4% in the placebo arm and 25.8% in the darbepoetin alfa arm—received 1 to 3 RBC units. And 17.1%—24.5% in the placebo arm and 13.4% in the darbepoetin alfa arm—received 4 or more RBC units.

Dosing

During the 24-week double-blind period of the study, 77% (37/48) of patients in the placebo arm and 79% (77/98) in the darbepoetin alfa arm received all 8 doses of treatment.

Sixteen percent (n=16) of patients in the darbepoetin alfa arm had a single dose reduction, and 2% (n=2) had 2 dose reductions. None of the patients in the placebo arm had a dose reduction.

Eleven percent of patients in the darbepoetin alfa arm had doses withheld due to increased hemoglobin. The dose was withheld once for 6 patients, twice for 4 patients, and 3 times for 1 patient. None of the placebo-treated patients had a dose withheld for this reason.

Ten percent (n=5) of placebo-treated patients and 2% (n=2) of darbepoetin alfa-treated patients had a dose withheld due to an AE. Two percent (n=1) and 3% (n=3) of patients, respectively, had a dose withheld for “other” reasons (noncompliance, investigator decision, and no investigational product on site).

During the 48-week open-label period of the study, 81% (102/126) of patients who received darbepoetin alfa increased their dose frequency from every 3 weeks to every 2 weeks. Dr Platzbecker said this suggests the optimal dose of the drug was not achieved during the 24-week double-blind period of the study.

Efficacy

During the 24-week double-blind period, there was a significant difference between the treatment arms with regard to RBC transfusions. The transfusion incidence was 59.2% (29/49) in the placebo arm and 36.1% (35/97) in the darbepoetin alfa arm (P=0.008).

During the 48-week open-label period, the incidence of RBC transfusion was 50.8% (64/126) among patients receiving darbepoetin alfa.

During the 24-week double-blind period, 11 patients (14.7%) in the darbepoetin alfa arm had an erythroid hematologic improvement (HI-E), but none of the patients in the placebo arm had such an improvement.

All 11 patients with HI-E had a baseline serum erythropoietin level less than 100 mU/mL, 1 of the patients had 2 RBC units transfused in the 16 weeks prior to randomization, but none had transfusions in the 8 weeks prior to randomization. Four of the patients had a dose withheld due to having hemoglobin levels greater than 12 g/dL.

During the 48-week open-label period, the HI-E rate was 34.7% (34/98) among patients receiving darbepoetin alfa.

Dr Platzbecker said the nature of the HI-E criteria likely underestimated the clinical benefit of darbepoetin alfa in this trial, and this was further complicated by the trial design. Specifically, hemoglobin was measured every 3 weeks, some patients may have had their doses reduced even if they were still anemic, and the optimal dose of darbepoetin alfa was likely not given during the double-blind period (as evidenced by the increase in doses during the open-label period).

For these reasons, Dr Platzbecker and his colleagues are exploring alternative response analyses to determine if there were additional patients who received a clinical benefit from darbepoetin alfa but did not meet HI-E criteria.

Safety

During the 24-week double-blind period, 4.2% (n=2) of patients in the placebo arm and 3.1% (n=3) in the darbepoetin alfa arm had AEs that led to treatment discontinuation. In the placebo arm, these events were pulmonary hypertension and renal failure. In the darbepoetin alfa arm, the events were pulmonary thrombosis, thrombocytopenia, and increased blast cell count.

The incidence of grade 3 or higher AEs was 27.1% (n=13) in the placebo arm and 15.3% (n=15) in the darbepoetin alfa arm. The incidence of grade 4 or higher AEs was 12.5% (n=6) and 5.1% (n=5), respectively. And the incidence of serious AEs was 16.7% (n=8) and 11.2% (n=11), respectively.

The incidence of fatal AEs was 4.2% (n=2) and 1% (n=1), respectively, but none of these were treatment-related. The deaths in the placebo arm were due to cardiac failure and cerebral hemorrhage, while the death in the darbepoetin alfa arm was due to hemorrhagic proctitis.

One patient in the darbepoetin alfa arm experienced a treatment-related serious AE.

AEs occurring at least 5% more frequently in the darbepoetin alfa arm than the placebo arm were fatigue (17.3% and 8.3%), pyrexia (9.2% and 2.1%), headache (7.1% and 2.1%), and myalgia (5.1% and 0%).

During the 48-week double-blind period, 7.9% (n=3) of patients formerly in the placebo arm and 3.4% (n=3) of patients formerly in the darbepoetin alfa arm had AEs that led to treatment discontinuation.

The incidence of grade 3 or higher AEs was 23.7% (n=9) and 31.0% (n=27), respectively. The incidence of grade 4 or higher AEs was 10.5% (n=4) and 10.3% (n=9), respectively. And the incidence of serious AEs was 18.4% (n=7) and 25.3% (n=22), respectively.

The incidence of fatal AEs was 2.6% (n=1) and 1.1% (n=1), respectively, but none of these were treatment-related. Two patients experienced a treatment-related serious AE—1 from each of the former treatment arms.

Uwe Platzbecker, MD

COPENHAGEN—The erythropoiesis-stimulating agent (ESA) darbepoetin alfa can provide a clinical benefit in patients with lower-risk myelodysplastic syndromes (MDS), a phase 3 trial suggests.

In the ARCADE trial, darbepoetin alfa significantly reduced the incidence of red blood cell (RBC) transfusions in patients with low- and intermediate-1 risk myelodysplastic syndrome (MDS), when compared to placebo.

The ESA also significantly improved erythroid response.

In addition, researchers said adverse events (AEs) were generally balanced between the darbepoetin alfa and placebo arms.

Uwe Platzbecker, MD, of University Hospital Carl Gustav Carus Dresden in Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S128). The ARCADE trial was sponsored by Amgen.

Dr Platzbecker noted that, although ESAs are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, the drugs are not widely approved for this indication.

So, in the ARCADE trial, he and his colleagues assessed darbepoetin alfa in patients with low- or intermediate-1 risk MDS who had not previously taken ESAs or biologic response modifiers.

The patients had hemoglobin levels ≤10 g/dL, endogenous erythropoietin levels ≤500 mU/mL, and low transfusion burden (<4 RBC units in each of 2 consecutive 8-week periods prior to randomization).

During a 24-week period, 147 patients received either darbepoetin alfa at 500 μg (n=97) or placebo (n=49) every 3 weeks. The ESA dose was withheld if patients’ hemoglobin was >12.0 g/dL and decreased if hemoglobin increased by >1.5 g/dL in 3 weeks without transfusion.

At week 25, when the primary and key secondary endpoints were assessed, patients underwent an end-of-treatment period visit. They could then enter a 48-week active treatment period and cross over to receive darbepoetin alfa, with dose escalation allowed beginning on week 31. Treatment continued until week 72 or 73, and patients continue to be assessed every 26 weeks, for a minimum of 3 years.

Patient characteristics

Dr Platzbecker said baseline demographic and disease characteristics were generally similar between the treatment arms. All patients were Caucasian, and about 55% were male. The median age was 74 (range, 67-79). About half of patients in each treatment arm belonged to the low-risk IPSS category.

In both arms, most patients had refractory cytopenia with multilineage dysplasia (38.8% in the placebo arm and 46.4% in the darbepoetin alfa arm). Patients also had refractory anemia with excess blasts-1 (20.4% and 13.4%, respectively), refractory anemia (26.5% and 9.3%), refractory anemia with ring sideroblasts (8.2% and 17.5%), 5q deletion (4.1% and 11.3%), unclassifiable MDS (2.0% and 1.0%), and MDS of an unknown type (0% and 1.0%).

In the 16 weeks before randomization, 58.2% of all patients—53.1% in the placebo arm and 60.8% in the darbepoetin alfa arm—did not have any RBC transfusions. About 25% (24.7%)—22.4% in the placebo arm and 25.8% in the darbepoetin alfa arm—received 1 to 3 RBC units. And 17.1%—24.5% in the placebo arm and 13.4% in the darbepoetin alfa arm—received 4 or more RBC units.

Dosing

During the 24-week double-blind period of the study, 77% (37/48) of patients in the placebo arm and 79% (77/98) in the darbepoetin alfa arm received all 8 doses of treatment.

Sixteen percent (n=16) of patients in the darbepoetin alfa arm had a single dose reduction, and 2% (n=2) had 2 dose reductions. None of the patients in the placebo arm had a dose reduction.

Eleven percent of patients in the darbepoetin alfa arm had doses withheld due to increased hemoglobin. The dose was withheld once for 6 patients, twice for 4 patients, and 3 times for 1 patient. None of the placebo-treated patients had a dose withheld for this reason.

Ten percent (n=5) of placebo-treated patients and 2% (n=2) of darbepoetin alfa-treated patients had a dose withheld due to an AE. Two percent (n=1) and 3% (n=3) of patients, respectively, had a dose withheld for “other” reasons (noncompliance, investigator decision, and no investigational product on site).

During the 48-week open-label period of the study, 81% (102/126) of patients who received darbepoetin alfa increased their dose frequency from every 3 weeks to every 2 weeks. Dr Platzbecker said this suggests the optimal dose of the drug was not achieved during the 24-week double-blind period of the study.

Efficacy

During the 24-week double-blind period, there was a significant difference between the treatment arms with regard to RBC transfusions. The transfusion incidence was 59.2% (29/49) in the placebo arm and 36.1% (35/97) in the darbepoetin alfa arm (P=0.008).

During the 48-week open-label period, the incidence of RBC transfusion was 50.8% (64/126) among patients receiving darbepoetin alfa.

During the 24-week double-blind period, 11 patients (14.7%) in the darbepoetin alfa arm had an erythroid hematologic improvement (HI-E), but none of the patients in the placebo arm had such an improvement.

All 11 patients with HI-E had a baseline serum erythropoietin level less than 100 mU/mL, 1 of the patients had 2 RBC units transfused in the 16 weeks prior to randomization, but none had transfusions in the 8 weeks prior to randomization. Four of the patients had a dose withheld due to having hemoglobin levels greater than 12 g/dL.

During the 48-week open-label period, the HI-E rate was 34.7% (34/98) among patients receiving darbepoetin alfa.

Dr Platzbecker said the nature of the HI-E criteria likely underestimated the clinical benefit of darbepoetin alfa in this trial, and this was further complicated by the trial design. Specifically, hemoglobin was measured every 3 weeks, some patients may have had their doses reduced even if they were still anemic, and the optimal dose of darbepoetin alfa was likely not given during the double-blind period (as evidenced by the increase in doses during the open-label period).

For these reasons, Dr Platzbecker and his colleagues are exploring alternative response analyses to determine if there were additional patients who received a clinical benefit from darbepoetin alfa but did not meet HI-E criteria.

Safety

During the 24-week double-blind period, 4.2% (n=2) of patients in the placebo arm and 3.1% (n=3) in the darbepoetin alfa arm had AEs that led to treatment discontinuation. In the placebo arm, these events were pulmonary hypertension and renal failure. In the darbepoetin alfa arm, the events were pulmonary thrombosis, thrombocytopenia, and increased blast cell count.

The incidence of grade 3 or higher AEs was 27.1% (n=13) in the placebo arm and 15.3% (n=15) in the darbepoetin alfa arm. The incidence of grade 4 or higher AEs was 12.5% (n=6) and 5.1% (n=5), respectively. And the incidence of serious AEs was 16.7% (n=8) and 11.2% (n=11), respectively.

The incidence of fatal AEs was 4.2% (n=2) and 1% (n=1), respectively, but none of these were treatment-related. The deaths in the placebo arm were due to cardiac failure and cerebral hemorrhage, while the death in the darbepoetin alfa arm was due to hemorrhagic proctitis.

One patient in the darbepoetin alfa arm experienced a treatment-related serious AE.

AEs occurring at least 5% more frequently in the darbepoetin alfa arm than the placebo arm were fatigue (17.3% and 8.3%), pyrexia (9.2% and 2.1%), headache (7.1% and 2.1%), and myalgia (5.1% and 0%).

During the 48-week double-blind period, 7.9% (n=3) of patients formerly in the placebo arm and 3.4% (n=3) of patients formerly in the darbepoetin alfa arm had AEs that led to treatment discontinuation.

The incidence of grade 3 or higher AEs was 23.7% (n=9) and 31.0% (n=27), respectively. The incidence of grade 4 or higher AEs was 10.5% (n=4) and 10.3% (n=9), respectively. And the incidence of serious AEs was 18.4% (n=7) and 25.3% (n=22), respectively.

The incidence of fatal AEs was 2.6% (n=1) and 1.1% (n=1), respectively, but none of these were treatment-related. Two patients experienced a treatment-related serious AE—1 from each of the former treatment arms.

Uwe Platzbecker, MD

COPENHAGEN—The erythropoiesis-stimulating agent (ESA) darbepoetin alfa can provide a clinical benefit in patients with lower-risk myelodysplastic syndromes (MDS), a phase 3 trial suggests.

In the ARCADE trial, darbepoetin alfa significantly reduced the incidence of red blood cell (RBC) transfusions in patients with low- and intermediate-1 risk myelodysplastic syndrome (MDS), when compared to placebo.

The ESA also significantly improved erythroid response.

In addition, researchers said adverse events (AEs) were generally balanced between the darbepoetin alfa and placebo arms.

Uwe Platzbecker, MD, of University Hospital Carl Gustav Carus Dresden in Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S128). The ARCADE trial was sponsored by Amgen.

Dr Platzbecker noted that, although ESAs are recommended in clinical guidelines to treat anemia in patients with lower-risk MDS, the drugs are not widely approved for this indication.

So, in the ARCADE trial, he and his colleagues assessed darbepoetin alfa in patients with low- or intermediate-1 risk MDS who had not previously taken ESAs or biologic response modifiers.

The patients had hemoglobin levels ≤10 g/dL, endogenous erythropoietin levels ≤500 mU/mL, and low transfusion burden (<4 RBC units in each of 2 consecutive 8-week periods prior to randomization).

During a 24-week period, 147 patients received either darbepoetin alfa at 500 μg (n=97) or placebo (n=49) every 3 weeks. The ESA dose was withheld if patients’ hemoglobin was >12.0 g/dL and decreased if hemoglobin increased by >1.5 g/dL in 3 weeks without transfusion.

At week 25, when the primary and key secondary endpoints were assessed, patients underwent an end-of-treatment period visit. They could then enter a 48-week active treatment period and cross over to receive darbepoetin alfa, with dose escalation allowed beginning on week 31. Treatment continued until week 72 or 73, and patients continue to be assessed every 26 weeks, for a minimum of 3 years.

Patient characteristics

Dr Platzbecker said baseline demographic and disease characteristics were generally similar between the treatment arms. All patients were Caucasian, and about 55% were male. The median age was 74 (range, 67-79). About half of patients in each treatment arm belonged to the low-risk IPSS category.

In both arms, most patients had refractory cytopenia with multilineage dysplasia (38.8% in the placebo arm and 46.4% in the darbepoetin alfa arm). Patients also had refractory anemia with excess blasts-1 (20.4% and 13.4%, respectively), refractory anemia (26.5% and 9.3%), refractory anemia with ring sideroblasts (8.2% and 17.5%), 5q deletion (4.1% and 11.3%), unclassifiable MDS (2.0% and 1.0%), and MDS of an unknown type (0% and 1.0%).

In the 16 weeks before randomization, 58.2% of all patients—53.1% in the placebo arm and 60.8% in the darbepoetin alfa arm—did not have any RBC transfusions. About 25% (24.7%)—22.4% in the placebo arm and 25.8% in the darbepoetin alfa arm—received 1 to 3 RBC units. And 17.1%—24.5% in the placebo arm and 13.4% in the darbepoetin alfa arm—received 4 or more RBC units.

Dosing

During the 24-week double-blind period of the study, 77% (37/48) of patients in the placebo arm and 79% (77/98) in the darbepoetin alfa arm received all 8 doses of treatment.

Sixteen percent (n=16) of patients in the darbepoetin alfa arm had a single dose reduction, and 2% (n=2) had 2 dose reductions. None of the patients in the placebo arm had a dose reduction.

Eleven percent of patients in the darbepoetin alfa arm had doses withheld due to increased hemoglobin. The dose was withheld once for 6 patients, twice for 4 patients, and 3 times for 1 patient. None of the placebo-treated patients had a dose withheld for this reason.

Ten percent (n=5) of placebo-treated patients and 2% (n=2) of darbepoetin alfa-treated patients had a dose withheld due to an AE. Two percent (n=1) and 3% (n=3) of patients, respectively, had a dose withheld for “other” reasons (noncompliance, investigator decision, and no investigational product on site).

During the 48-week open-label period of the study, 81% (102/126) of patients who received darbepoetin alfa increased their dose frequency from every 3 weeks to every 2 weeks. Dr Platzbecker said this suggests the optimal dose of the drug was not achieved during the 24-week double-blind period of the study.

Efficacy

During the 24-week double-blind period, there was a significant difference between the treatment arms with regard to RBC transfusions. The transfusion incidence was 59.2% (29/49) in the placebo arm and 36.1% (35/97) in the darbepoetin alfa arm (P=0.008).

During the 48-week open-label period, the incidence of RBC transfusion was 50.8% (64/126) among patients receiving darbepoetin alfa.

During the 24-week double-blind period, 11 patients (14.7%) in the darbepoetin alfa arm had an erythroid hematologic improvement (HI-E), but none of the patients in the placebo arm had such an improvement.

All 11 patients with HI-E had a baseline serum erythropoietin level less than 100 mU/mL, 1 of the patients had 2 RBC units transfused in the 16 weeks prior to randomization, but none had transfusions in the 8 weeks prior to randomization. Four of the patients had a dose withheld due to having hemoglobin levels greater than 12 g/dL.

During the 48-week open-label period, the HI-E rate was 34.7% (34/98) among patients receiving darbepoetin alfa.

Dr Platzbecker said the nature of the HI-E criteria likely underestimated the clinical benefit of darbepoetin alfa in this trial, and this was further complicated by the trial design. Specifically, hemoglobin was measured every 3 weeks, some patients may have had their doses reduced even if they were still anemic, and the optimal dose of darbepoetin alfa was likely not given during the double-blind period (as evidenced by the increase in doses during the open-label period).

For these reasons, Dr Platzbecker and his colleagues are exploring alternative response analyses to determine if there were additional patients who received a clinical benefit from darbepoetin alfa but did not meet HI-E criteria.

Safety

During the 24-week double-blind period, 4.2% (n=2) of patients in the placebo arm and 3.1% (n=3) in the darbepoetin alfa arm had AEs that led to treatment discontinuation. In the placebo arm, these events were pulmonary hypertension and renal failure. In the darbepoetin alfa arm, the events were pulmonary thrombosis, thrombocytopenia, and increased blast cell count.

The incidence of grade 3 or higher AEs was 27.1% (n=13) in the placebo arm and 15.3% (n=15) in the darbepoetin alfa arm. The incidence of grade 4 or higher AEs was 12.5% (n=6) and 5.1% (n=5), respectively. And the incidence of serious AEs was 16.7% (n=8) and 11.2% (n=11), respectively.

The incidence of fatal AEs was 4.2% (n=2) and 1% (n=1), respectively, but none of these were treatment-related. The deaths in the placebo arm were due to cardiac failure and cerebral hemorrhage, while the death in the darbepoetin alfa arm was due to hemorrhagic proctitis.

One patient in the darbepoetin alfa arm experienced a treatment-related serious AE.

AEs occurring at least 5% more frequently in the darbepoetin alfa arm than the placebo arm were fatigue (17.3% and 8.3%), pyrexia (9.2% and 2.1%), headache (7.1% and 2.1%), and myalgia (5.1% and 0%).

During the 48-week double-blind period, 7.9% (n=3) of patients formerly in the placebo arm and 3.4% (n=3) of patients formerly in the darbepoetin alfa arm had AEs that led to treatment discontinuation.

The incidence of grade 3 or higher AEs was 23.7% (n=9) and 31.0% (n=27), respectively. The incidence of grade 4 or higher AEs was 10.5% (n=4) and 10.3% (n=9), respectively. And the incidence of serious AEs was 18.4% (n=7) and 25.3% (n=22), respectively.

The incidence of fatal AEs was 2.6% (n=1) and 1.1% (n=1), respectively, but none of these were treatment-related. Two patients experienced a treatment-related serious AE—1 from each of the former treatment arms.

Platelets (purple) in a thrombus

Image by Andre E.X. Brown

Antiplatelet drugs can significantly reduce amyloid plaques in cerebral vessels of transgenic mice with Alzheimer’s disease, according to new research.

The study revealed a mechanism for direct involvement of platelets in the progression of Alzheimer’s disease, and investigators believe this could be of great importance for the treatment of Alzheimer’s patients.

Alzheimer’s disease is characterized by the formation of amyloid aggregates and deposits of amyloid in the brain. The amyloid deposits damage the structure and function of nerve tissue in the brain and lead to the loss of neuronal cells and cognitive capability.

Amyloid deposits in Alzheimer’s disease occur not only in the brain parenchyma, but also in blood vessels in the brain. The current study, published in Science Signaling, deals with the vascular form of the disease.

Previous research demonstrated that platelets attach to amyloid deposits in the vessel wall, which leads to ongoing platelet activation in mice. The platelets then form a hemostatic plug, which occludes vessels in the brain and leads to insufficient perfusion of the surrounding tissue.

Investigators have now determined that the protein amyloid-ß binds to a specific integrin on the platelet surface that is important for the aggregation of platelets.

This binding induces the release of adenosine diphosphate and the chaperone protein clusterin and supports the formation of amyloid plaques.

In cell culture experiments, the investigators analyzed platelets from 5 patients with Glanzmann’s thrombasthenia, a hereditary defect of platelet activation, and found no amyloid plaques.

The team then treated Alzheimer’s transgenic mice with the antiplatelet agent clopidogrel. The mice exhibited reduced platelet activation and significantly reduced amyloid plaque formation, which improved the perfusion of the brain during the 3-month treatment with the drug.

The investigators suggest that antiplatelet therapy may alleviate fibril formation in cerebral vessels of Alzheimer’s disease patients.

Platelets (purple) in a thrombus

Image by Andre E.X. Brown

Antiplatelet drugs can significantly reduce amyloid plaques in cerebral vessels of transgenic mice with Alzheimer’s disease, according to new research.

The study revealed a mechanism for direct involvement of platelets in the progression of Alzheimer’s disease, and investigators believe this could be of great importance for the treatment of Alzheimer’s patients.

Alzheimer’s disease is characterized by the formation of amyloid aggregates and deposits of amyloid in the brain. The amyloid deposits damage the structure and function of nerve tissue in the brain and lead to the loss of neuronal cells and cognitive capability.

Amyloid deposits in Alzheimer’s disease occur not only in the brain parenchyma, but also in blood vessels in the brain. The current study, published in Science Signaling, deals with the vascular form of the disease.

Previous research demonstrated that platelets attach to amyloid deposits in the vessel wall, which leads to ongoing platelet activation in mice. The platelets then form a hemostatic plug, which occludes vessels in the brain and leads to insufficient perfusion of the surrounding tissue.

Investigators have now determined that the protein amyloid-ß binds to a specific integrin on the platelet surface that is important for the aggregation of platelets.

This binding induces the release of adenosine diphosphate and the chaperone protein clusterin and supports the formation of amyloid plaques.

In cell culture experiments, the investigators analyzed platelets from 5 patients with Glanzmann’s thrombasthenia, a hereditary defect of platelet activation, and found no amyloid plaques.

The team then treated Alzheimer’s transgenic mice with the antiplatelet agent clopidogrel. The mice exhibited reduced platelet activation and significantly reduced amyloid plaque formation, which improved the perfusion of the brain during the 3-month treatment with the drug.

The investigators suggest that antiplatelet therapy may alleviate fibril formation in cerebral vessels of Alzheimer’s disease patients.

Platelets (purple) in a thrombus

Image by Andre E.X. Brown

Antiplatelet drugs can significantly reduce amyloid plaques in cerebral vessels of transgenic mice with Alzheimer’s disease, according to new research.

The study revealed a mechanism for direct involvement of platelets in the progression of Alzheimer’s disease, and investigators believe this could be of great importance for the treatment of Alzheimer’s patients.

Alzheimer’s disease is characterized by the formation of amyloid aggregates and deposits of amyloid in the brain. The amyloid deposits damage the structure and function of nerve tissue in the brain and lead to the loss of neuronal cells and cognitive capability.

Amyloid deposits in Alzheimer’s disease occur not only in the brain parenchyma, but also in blood vessels in the brain. The current study, published in Science Signaling, deals with the vascular form of the disease.

Previous research demonstrated that platelets attach to amyloid deposits in the vessel wall, which leads to ongoing platelet activation in mice. The platelets then form a hemostatic plug, which occludes vessels in the brain and leads to insufficient perfusion of the surrounding tissue.

Investigators have now determined that the protein amyloid-ß binds to a specific integrin on the platelet surface that is important for the aggregation of platelets.

This binding induces the release of adenosine diphosphate and the chaperone protein clusterin and supports the formation of amyloid plaques.

In cell culture experiments, the investigators analyzed platelets from 5 patients with Glanzmann’s thrombasthenia, a hereditary defect of platelet activation, and found no amyloid plaques.

The team then treated Alzheimer’s transgenic mice with the antiplatelet agent clopidogrel. The mice exhibited reduced platelet activation and significantly reduced amyloid plaque formation, which improved the perfusion of the brain during the 3-month treatment with the drug.

The investigators suggest that antiplatelet therapy may alleviate fibril formation in cerebral vessels of Alzheimer’s disease patients.

LONDON – The first European guidelines developed to help the transition of young people from pediatric to adult rheumatology care within Europe were announced at the European Congress of Rheumatology.

The key aim of the guidelines, which have been jointly written by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS), is to make the transition process more consistent across rheumatology practices throughout Europe, which in turn should help to ensure both the continuity and the quality of clinical care, explained Dr. Helen E. Fosterof Newcastle (England) University.

“There is evidence that there has been a long-standing problem of young people growing up with their condition moving to adult care and either falling between the services or being lost to follow-up, or there has not been continuity of care,” she said in an interview ahead of presenting the new EULAR/PReS guidelines at the congress.

“All in all, that’s translated into poorer health outcomes for young people,” said Dr. Foster, who was one of the main convenors of the EULAR/PReS Working Party for Transitional Care Management for Adolescents and Young People. 

The premise is to try to provide practical recommendations that clinicians can use to help young people in their care from the age of 11 years and older as they get ready for the transfer to adult services. The latter process can occur anywhere from 16 to 19 years of age, Dr. Foster said, but it is important to try start the transition process early and get young people more involved and responsible for their own care.

“The idea is that young people are supported to be in control of their condition, that they can cope with being seen on their own in clinic, that they are getting on with their lives, and ultimately that they have a better outcome, which includes becoming healthy, getting a job, living independently, and having a family,” she said. The age at transfer is flexible and needs to fit with the young person’s home and school life. Ideally, it occurs at a time when their disease and medication are stable, they are attending routine appointments, and generally able to be independent and cope with their condition.

EULAR/PReS transition guidelines: 12 recommendations

• Access to high-quality coordinated transition care services should be available to all young people.

• Transition should ‘start early’ (11 years of age) or directly after diagnosis.

• Direct communication is needed between young people and their families and pediatric and adult care providers.

• Each young person should have an individualized transition plan.

• There should be a written transition policy within all relevant services; this should be regularly agreed and updated.

• The multidisciplinary team involved in transitional care should be clearly defined in a written document.

• Transition services should address the complexity of adolescent and young adult development.

• There must be an agreed upon and written transfer document.

• Health care teams should be given appropriate training in adolescent and young adult rheumatic diseases.

• Secure funding is needed for uninterrupted clinical care and transition into adult services.

• An open digital platform should host the recommendations and support tools and information.

• More evidence is needed to demonstrate the outcomes of the transition to adult services.

Developing the guidelines

Together with Dr. Kirsten Minden of the German Rheumatism Research Centre Berlin (DRFZ), Dr. Foster chaired the international, multidisciplinary EULAR/PReS Working Party to review existing national and international guidelines, consensus statements, and other supporting evidence on transitional care management in childhood-onset rheumatic illness.

The remit was to develop recommendations to facilitate optimal transitional care management in rheumatology across different European countries. As such, the recommendations cover both the ideal situation as well as the bare minimum requirements to hopefully allow widespread adoption. To this end, the working party performed a systematic literature review according to EULAR standard operating procedures. They developed a set of 12 recommendations based on the evidence they reviewed.

There are 47 different health systems within Europe, all running according to different health policies set by different governments, Dr. Minden observed. In fact, only a handful of countries have specific transition care policies or pathways, so the aim was to try to develop recommendations that would work across the board while giving some ideas on how to improve existing strategies further.

She noted that some examples of existing transition programs are “Growing up and moving on” in the United Kingdom (Pediatr Transplant. 2005;9:364-72), “On your own feet ahead” in the Netherlands (BMC Health Serv Res. 2014;14:47), and “Devices for Optimization of Transfer and Transition of Adolescents with Rheumatic Disorders (DON’T RETARD)” in Belgium (Rheumatology [Oxford]. 2016;55:133-42). Of these, two are specific to the transition of young people with juvenile idiopathic arthritis (JIA) and one is for rheumatologic conditions in general.

Core elements of these programs are the need to provide written information and have a transition care plan, the allocation of a dedicated transition coordinator, and an individualized transition plan for each patient, Dr. Minden said. These elements are also part of the EULAR/PReS transition guidelines.

One of the issues to be addressed, however, is whether these transition programs actually work in the long term. “Transitional care services in rheumatology are beginning to happen and their further development can surely be facilitated by the provision of tool kits and resources for health care providers and patients,” she noted. Some of the tools already exist, so the challenge now is to get these available to all so that there can be a wider dissemination of knowledge.

The North American perspective

Both the American Academy of Pediatrics and the Canadian Pediatric Society have issued general guidance on how to transition young people from pediatric to adult services, said Dr. Lori. B. Tucker, a pediatric specialist working at BC Children’s Hospital in Vancouver, which runs the ON TRAC (Transitioning Responsibly to Adult Care) program. This is a province-wide program aimed at supporting young people between the ages of 12 and 24 years with chronic health conditions and their families to transition from pediatric to adult health care services.

The ON TRAC program includes online and mobile-enabled checklists that can be used with young people and their families, although Dr. Tucker noted that the program had perhaps not been as successful as had been hoped. Another Canadian initiative specific to rheumatology practice is the RACER (Readiness for Adult Care in Rheumatology) questionnaire. This was developed to assess how ready young people with chronic ailments were to transition to adult service.

Dr. Tucker also highlighted the YARD (Young Adult Rheumatic Diseases) clinic at her institution, set up for those aged 18 years or older with a definite diagnosis of rheumatic disease. Parents are not allowed within the clinic so as to enable young adults to take responsibility for their overall care and collaborate with their health care providers. The clinic provides education, assistance with separation independence, and other issues pertinent to this young population of patients, and it also aims to encourage adherence to appointments and treatments.

“Collaboration between pediatric rheumatologists and adult colleagues is critical to improve the outcomes of young adults with rheumatic diseases,” Dr. Tucker said. She added, “Better articulated guidelines for transition care and use of new tools have great potential to improve the care of these patients ‘lost in-between.’ ”

Why the need for the EULAR/PReS recommendations?

Dr. Foster noted that, in many countries, there is a natural break between pediatric and adult care, with young people often moving from one center to another, perhaps in another part of the country. An important part of the transition process is therefore ensuring that there are appropriately trained staff members and good communication between centers to ensure that young people don’t get lost during the move. 

“This is everyone’s business,” Dr. Foster said at the congress. “It is a shared responsibility to get it right.” That means adult and pediatric health care teams work together. Care needs to be “holistic,” she added, and cover medical, psychosocial, vocational issues, and be “developmentally appropriate throughout.” Young people also need to be involved from the start of the process, beginning early and continuing into young adulthood.

The recommendations aim to be flexible so that they can be widely implemented by health care teams throughout Europe. “It is not ‘one size fits all,” Dr. Foster acknowledged in the interview, noting the importance of being realistic and recognizing the differences between health systems, resources, and access across Europe. 

Dr. Foster, who trained in adult rheumatology before turning to pediatric rheumatology, noted that there are existing resources that can be used and although funding will be an issue on some levels, there are things that can be done by using existing tools and resources.

“We don’t want to reinvent the wheel. We want to share best practice and resources,” she said. Indeed, one of the recommendations is that all the guidelines and all the resources used to develop them are made publicly available via an electronic platform so that anybody involved in the care of a young person with rheumatic disease, as well as the young person and their family, can access them.

“Transitional care is key to improving long-term outcomes for young people with rheumatic disease,” Dr. Foster concluded. The EULAR/PReS transition care management guidelines have been developed with the engagement of all relevant stakeholders, she said, so they should be widely applicable and “important levers for change” throughout Europe. “Implementation will require funding, but also our will and energy to make them actually work in practice.”

The EULAR/PReS transition guidelines are being finalized and will be published soon in Annals of the Rheumatic Diseases.

Dr. Foster, Dr. Minden, and Dr. Tucker had no disclosures relevant to the development of the recommendations.  

[email protected]

LONDON – The first European guidelines developed to help the transition of young people from pediatric to adult rheumatology care within Europe were announced at the European Congress of Rheumatology.

The key aim of the guidelines, which have been jointly written by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS), is to make the transition process more consistent across rheumatology practices throughout Europe, which in turn should help to ensure both the continuity and the quality of clinical care, explained Dr. Helen E. Fosterof Newcastle (England) University.

“There is evidence that there has been a long-standing problem of young people growing up with their condition moving to adult care and either falling between the services or being lost to follow-up, or there has not been continuity of care,” she said in an interview ahead of presenting the new EULAR/PReS guidelines at the congress.

“All in all, that’s translated into poorer health outcomes for young people,” said Dr. Foster, who was one of the main convenors of the EULAR/PReS Working Party for Transitional Care Management for Adolescents and Young People. 

The premise is to try to provide practical recommendations that clinicians can use to help young people in their care from the age of 11 years and older as they get ready for the transfer to adult services. The latter process can occur anywhere from 16 to 19 years of age, Dr. Foster said, but it is important to try start the transition process early and get young people more involved and responsible for their own care.

“The idea is that young people are supported to be in control of their condition, that they can cope with being seen on their own in clinic, that they are getting on with their lives, and ultimately that they have a better outcome, which includes becoming healthy, getting a job, living independently, and having a family,” she said. The age at transfer is flexible and needs to fit with the young person’s home and school life. Ideally, it occurs at a time when their disease and medication are stable, they are attending routine appointments, and generally able to be independent and cope with their condition.

EULAR/PReS transition guidelines: 12 recommendations

• Access to high-quality coordinated transition care services should be available to all young people.

• Transition should ‘start early’ (11 years of age) or directly after diagnosis.

• Direct communication is needed between young people and their families and pediatric and adult care providers.

• Each young person should have an individualized transition plan.

• There should be a written transition policy within all relevant services; this should be regularly agreed and updated.

• The multidisciplinary team involved in transitional care should be clearly defined in a written document.

• Transition services should address the complexity of adolescent and young adult development.

• There must be an agreed upon and written transfer document.

• Health care teams should be given appropriate training in adolescent and young adult rheumatic diseases.

• Secure funding is needed for uninterrupted clinical care and transition into adult services.

• An open digital platform should host the recommendations and support tools and information.

• More evidence is needed to demonstrate the outcomes of the transition to adult services.

Developing the guidelines

Together with Dr. Kirsten Minden of the German Rheumatism Research Centre Berlin (DRFZ), Dr. Foster chaired the international, multidisciplinary EULAR/PReS Working Party to review existing national and international guidelines, consensus statements, and other supporting evidence on transitional care management in childhood-onset rheumatic illness.

The remit was to develop recommendations to facilitate optimal transitional care management in rheumatology across different European countries. As such, the recommendations cover both the ideal situation as well as the bare minimum requirements to hopefully allow widespread adoption. To this end, the working party performed a systematic literature review according to EULAR standard operating procedures. They developed a set of 12 recommendations based on the evidence they reviewed.

There are 47 different health systems within Europe, all running according to different health policies set by different governments, Dr. Minden observed. In fact, only a handful of countries have specific transition care policies or pathways, so the aim was to try to develop recommendations that would work across the board while giving some ideas on how to improve existing strategies further.

She noted that some examples of existing transition programs are “Growing up and moving on” in the United Kingdom (Pediatr Transplant. 2005;9:364-72), “On your own feet ahead” in the Netherlands (BMC Health Serv Res. 2014;14:47), and “Devices for Optimization of Transfer and Transition of Adolescents with Rheumatic Disorders (DON’T RETARD)” in Belgium (Rheumatology [Oxford]. 2016;55:133-42). Of these, two are specific to the transition of young people with juvenile idiopathic arthritis (JIA) and one is for rheumatologic conditions in general.

Core elements of these programs are the need to provide written information and have a transition care plan, the allocation of a dedicated transition coordinator, and an individualized transition plan for each patient, Dr. Minden said. These elements are also part of the EULAR/PReS transition guidelines.

One of the issues to be addressed, however, is whether these transition programs actually work in the long term. “Transitional care services in rheumatology are beginning to happen and their further development can surely be facilitated by the provision of tool kits and resources for health care providers and patients,” she noted. Some of the tools already exist, so the challenge now is to get these available to all so that there can be a wider dissemination of knowledge.

The North American perspective

Both the American Academy of Pediatrics and the Canadian Pediatric Society have issued general guidance on how to transition young people from pediatric to adult services, said Dr. Lori. B. Tucker, a pediatric specialist working at BC Children’s Hospital in Vancouver, which runs the ON TRAC (Transitioning Responsibly to Adult Care) program. This is a province-wide program aimed at supporting young people between the ages of 12 and 24 years with chronic health conditions and their families to transition from pediatric to adult health care services.

The ON TRAC program includes online and mobile-enabled checklists that can be used with young people and their families, although Dr. Tucker noted that the program had perhaps not been as successful as had been hoped. Another Canadian initiative specific to rheumatology practice is the RACER (Readiness for Adult Care in Rheumatology) questionnaire. This was developed to assess how ready young people with chronic ailments were to transition to adult service.

Dr. Tucker also highlighted the YARD (Young Adult Rheumatic Diseases) clinic at her institution, set up for those aged 18 years or older with a definite diagnosis of rheumatic disease. Parents are not allowed within the clinic so as to enable young adults to take responsibility for their overall care and collaborate with their health care providers. The clinic provides education, assistance with separation independence, and other issues pertinent to this young population of patients, and it also aims to encourage adherence to appointments and treatments.

“Collaboration between pediatric rheumatologists and adult colleagues is critical to improve the outcomes of young adults with rheumatic diseases,” Dr. Tucker said. She added, “Better articulated guidelines for transition care and use of new tools have great potential to improve the care of these patients ‘lost in-between.’ ”

Why the need for the EULAR/PReS recommendations?

Dr. Foster noted that, in many countries, there is a natural break between pediatric and adult care, with young people often moving from one center to another, perhaps in another part of the country. An important part of the transition process is therefore ensuring that there are appropriately trained staff members and good communication between centers to ensure that young people don’t get lost during the move. 

“This is everyone’s business,” Dr. Foster said at the congress. “It is a shared responsibility to get it right.” That means adult and pediatric health care teams work together. Care needs to be “holistic,” she added, and cover medical, psychosocial, vocational issues, and be “developmentally appropriate throughout.” Young people also need to be involved from the start of the process, beginning early and continuing into young adulthood.

The recommendations aim to be flexible so that they can be widely implemented by health care teams throughout Europe. “It is not ‘one size fits all,” Dr. Foster acknowledged in the interview, noting the importance of being realistic and recognizing the differences between health systems, resources, and access across Europe. 

Dr. Foster, who trained in adult rheumatology before turning to pediatric rheumatology, noted that there are existing resources that can be used and although funding will be an issue on some levels, there are things that can be done by using existing tools and resources.

“We don’t want to reinvent the wheel. We want to share best practice and resources,” she said. Indeed, one of the recommendations is that all the guidelines and all the resources used to develop them are made publicly available via an electronic platform so that anybody involved in the care of a young person with rheumatic disease, as well as the young person and their family, can access them.

“Transitional care is key to improving long-term outcomes for young people with rheumatic disease,” Dr. Foster concluded. The EULAR/PReS transition care management guidelines have been developed with the engagement of all relevant stakeholders, she said, so they should be widely applicable and “important levers for change” throughout Europe. “Implementation will require funding, but also our will and energy to make them actually work in practice.”

The EULAR/PReS transition guidelines are being finalized and will be published soon in Annals of the Rheumatic Diseases.

Dr. Foster, Dr. Minden, and Dr. Tucker had no disclosures relevant to the development of the recommendations.  

[email protected]

LONDON – The first European guidelines developed to help the transition of young people from pediatric to adult rheumatology care within Europe were announced at the European Congress of Rheumatology.

The key aim of the guidelines, which have been jointly written by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS), is to make the transition process more consistent across rheumatology practices throughout Europe, which in turn should help to ensure both the continuity and the quality of clinical care, explained Dr. Helen E. Fosterof Newcastle (England) University.

“There is evidence that there has been a long-standing problem of young people growing up with their condition moving to adult care and either falling between the services or being lost to follow-up, or there has not been continuity of care,” she said in an interview ahead of presenting the new EULAR/PReS guidelines at the congress.

“All in all, that’s translated into poorer health outcomes for young people,” said Dr. Foster, who was one of the main convenors of the EULAR/PReS Working Party for Transitional Care Management for Adolescents and Young People. 

The premise is to try to provide practical recommendations that clinicians can use to help young people in their care from the age of 11 years and older as they get ready for the transfer to adult services. The latter process can occur anywhere from 16 to 19 years of age, Dr. Foster said, but it is important to try start the transition process early and get young people more involved and responsible for their own care.

“The idea is that young people are supported to be in control of their condition, that they can cope with being seen on their own in clinic, that they are getting on with their lives, and ultimately that they have a better outcome, which includes becoming healthy, getting a job, living independently, and having a family,” she said. The age at transfer is flexible and needs to fit with the young person’s home and school life. Ideally, it occurs at a time when their disease and medication are stable, they are attending routine appointments, and generally able to be independent and cope with their condition.

EULAR/PReS transition guidelines: 12 recommendations

• Access to high-quality coordinated transition care services should be available to all young people.

• Transition should ‘start early’ (11 years of age) or directly after diagnosis.

• Direct communication is needed between young people and their families and pediatric and adult care providers.

• Each young person should have an individualized transition plan.

• There should be a written transition policy within all relevant services; this should be regularly agreed and updated.

• The multidisciplinary team involved in transitional care should be clearly defined in a written document.

• Transition services should address the complexity of adolescent and young adult development.

• There must be an agreed upon and written transfer document.

• Health care teams should be given appropriate training in adolescent and young adult rheumatic diseases.

• Secure funding is needed for uninterrupted clinical care and transition into adult services.

• An open digital platform should host the recommendations and support tools and information.

• More evidence is needed to demonstrate the outcomes of the transition to adult services.

Developing the guidelines

Together with Dr. Kirsten Minden of the German Rheumatism Research Centre Berlin (DRFZ), Dr. Foster chaired the international, multidisciplinary EULAR/PReS Working Party to review existing national and international guidelines, consensus statements, and other supporting evidence on transitional care management in childhood-onset rheumatic illness.

The remit was to develop recommendations to facilitate optimal transitional care management in rheumatology across different European countries. As such, the recommendations cover both the ideal situation as well as the bare minimum requirements to hopefully allow widespread adoption. To this end, the working party performed a systematic literature review according to EULAR standard operating procedures. They developed a set of 12 recommendations based on the evidence they reviewed.

There are 47 different health systems within Europe, all running according to different health policies set by different governments, Dr. Minden observed. In fact, only a handful of countries have specific transition care policies or pathways, so the aim was to try to develop recommendations that would work across the board while giving some ideas on how to improve existing strategies further.

She noted that some examples of existing transition programs are “Growing up and moving on” in the United Kingdom (Pediatr Transplant. 2005;9:364-72), “On your own feet ahead” in the Netherlands (BMC Health Serv Res. 2014;14:47), and “Devices for Optimization of Transfer and Transition of Adolescents with Rheumatic Disorders (DON’T RETARD)” in Belgium (Rheumatology [Oxford]. 2016;55:133-42). Of these, two are specific to the transition of young people with juvenile idiopathic arthritis (JIA) and one is for rheumatologic conditions in general.

Core elements of these programs are the need to provide written information and have a transition care plan, the allocation of a dedicated transition coordinator, and an individualized transition plan for each patient, Dr. Minden said. These elements are also part of the EULAR/PReS transition guidelines.

One of the issues to be addressed, however, is whether these transition programs actually work in the long term. “Transitional care services in rheumatology are beginning to happen and their further development can surely be facilitated by the provision of tool kits and resources for health care providers and patients,” she noted. Some of the tools already exist, so the challenge now is to get these available to all so that there can be a wider dissemination of knowledge.

The North American perspective

Both the American Academy of Pediatrics and the Canadian Pediatric Society have issued general guidance on how to transition young people from pediatric to adult services, said Dr. Lori. B. Tucker, a pediatric specialist working at BC Children’s Hospital in Vancouver, which runs the ON TRAC (Transitioning Responsibly to Adult Care) program. This is a province-wide program aimed at supporting young people between the ages of 12 and 24 years with chronic health conditions and their families to transition from pediatric to adult health care services.

The ON TRAC program includes online and mobile-enabled checklists that can be used with young people and their families, although Dr. Tucker noted that the program had perhaps not been as successful as had been hoped. Another Canadian initiative specific to rheumatology practice is the RACER (Readiness for Adult Care in Rheumatology) questionnaire. This was developed to assess how ready young people with chronic ailments were to transition to adult service.

Dr. Tucker also highlighted the YARD (Young Adult Rheumatic Diseases) clinic at her institution, set up for those aged 18 years or older with a definite diagnosis of rheumatic disease. Parents are not allowed within the clinic so as to enable young adults to take responsibility for their overall care and collaborate with their health care providers. The clinic provides education, assistance with separation independence, and other issues pertinent to this young population of patients, and it also aims to encourage adherence to appointments and treatments.

“Collaboration between pediatric rheumatologists and adult colleagues is critical to improve the outcomes of young adults with rheumatic diseases,” Dr. Tucker said. She added, “Better articulated guidelines for transition care and use of new tools have great potential to improve the care of these patients ‘lost in-between.’ ”

Why the need for the EULAR/PReS recommendations?

Dr. Foster noted that, in many countries, there is a natural break between pediatric and adult care, with young people often moving from one center to another, perhaps in another part of the country. An important part of the transition process is therefore ensuring that there are appropriately trained staff members and good communication between centers to ensure that young people don’t get lost during the move. 

“This is everyone’s business,” Dr. Foster said at the congress. “It is a shared responsibility to get it right.” That means adult and pediatric health care teams work together. Care needs to be “holistic,” she added, and cover medical, psychosocial, vocational issues, and be “developmentally appropriate throughout.” Young people also need to be involved from the start of the process, beginning early and continuing into young adulthood.

The recommendations aim to be flexible so that they can be widely implemented by health care teams throughout Europe. “It is not ‘one size fits all,” Dr. Foster acknowledged in the interview, noting the importance of being realistic and recognizing the differences between health systems, resources, and access across Europe. 

Dr. Foster, who trained in adult rheumatology before turning to pediatric rheumatology, noted that there are existing resources that can be used and although funding will be an issue on some levels, there are things that can be done by using existing tools and resources.

“We don’t want to reinvent the wheel. We want to share best practice and resources,” she said. Indeed, one of the recommendations is that all the guidelines and all the resources used to develop them are made publicly available via an electronic platform so that anybody involved in the care of a young person with rheumatic disease, as well as the young person and their family, can access them.

“Transitional care is key to improving long-term outcomes for young people with rheumatic disease,” Dr. Foster concluded. The EULAR/PReS transition care management guidelines have been developed with the engagement of all relevant stakeholders, she said, so they should be widely applicable and “important levers for change” throughout Europe. “Implementation will require funding, but also our will and energy to make them actually work in practice.”

The EULAR/PReS transition guidelines are being finalized and will be published soon in Annals of the Rheumatic Diseases.

Dr. Foster, Dr. Minden, and Dr. Tucker had no disclosures relevant to the development of the recommendations.  

[email protected]

Hot off the presses, a new so-called “second skin” is being redeveloped and rebranded for use in both cosmetic and medical dermatology. But what is this substance, and will it hold up to all the claims the manufacturer and research team suggest?

Recently described in Nature Materials, the liquid polymer developed by chemical engineers at MIT is a synthetic, adherent silicone-based film that lies perfectly invisibly on the skin – providing a pulling or temporary tightening of the skin. The product was initially marketed by the company Living Proof as “Neotensil” [an acronym for (Neo) new, (T) transforming, (E) elastic, (N) non-invasive, (S) supportive, (I) invisible, and immediate (L) layer solution]. When applied to the area under the eye, the product creates a so-called “Spanx” effect or tightening of periorbital skin.

The material – called XPL – is delivered in a two-step sequential process. First, a polysiloxane cream is applied to the skin, followed by a platinum catalyst that induces the polymer to harden and tighten the skin underneath. The product uses patented Strateris technology, which is described as creating invisible “shapewear” for the eye; a film that tightens, smooths, and lifts the appearance of skin for up to 24 hours. It was briefly on the market in 2014-2015, then taken off the market to be redeveloped.

Does it work? Yes. Although it takes about an hour to take effect, the clinical results are jaw dropping. However, it also has its drawbacks. The polymer – which hardens within 2 minutes – must be applied to clean skin, with no creams or makeup whatsoever. And makeup cannot be applied over the treated area either, as the area looks irregular and uneven with makeup. This is a very difficult obstacle to overcome for many female patients.

Additionally, to take off the product, the polymer must be dissolved with a special chemical remover that is packaged with the product. Without this key component, it is very difficult and very irritating to remove. Although none of the patients I have used this product on have developed allergic reactions, any synthetic polymer, particularly one with adherent properties, has the potential to be an irritant and/or an allergen. Long-term clinical trials are needed to both validate its efficacy and side-effect profile.

The potential for clinical uses is vast. The product has been shown to provide a synthetic skin barrier that minimizes transepidermal water loss, improving skin hydration. Its uses in burns, atopic dermatitis, bullous disease, and psoriasis could help those with altered skin-barrier function. The researchers are also hoping to use this product for targeted drug delivery and for UV protection.

After a decade of research, the MIT team has developed a skinlike material that is invisible and mimics both the mechanical and elastic properties of the skin. Future clinical studies are essential to evaluating its broad applicability in both dermatology and general medicine.

1. Nature Materials 2016. doi:10.1038/nmat4635.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Dr. Talakoub has no disclosures related to the product. Write to them at [email protected].

Hot off the presses, a new so-called “second skin” is being redeveloped and rebranded for use in both cosmetic and medical dermatology. But what is this substance, and will it hold up to all the claims the manufacturer and research team suggest?

Recently described in Nature Materials, the liquid polymer developed by chemical engineers at MIT is a synthetic, adherent silicone-based film that lies perfectly invisibly on the skin – providing a pulling or temporary tightening of the skin. The product was initially marketed by the company Living Proof as “Neotensil” [an acronym for (Neo) new, (T) transforming, (E) elastic, (N) non-invasive, (S) supportive, (I) invisible, and immediate (L) layer solution]. When applied to the area under the eye, the product creates a so-called “Spanx” effect or tightening of periorbital skin.

The material – called XPL – is delivered in a two-step sequential process. First, a polysiloxane cream is applied to the skin, followed by a platinum catalyst that induces the polymer to harden and tighten the skin underneath. The product uses patented Strateris technology, which is described as creating invisible “shapewear” for the eye; a film that tightens, smooths, and lifts the appearance of skin for up to 24 hours. It was briefly on the market in 2014-2015, then taken off the market to be redeveloped.

Does it work? Yes. Although it takes about an hour to take effect, the clinical results are jaw dropping. However, it also has its drawbacks. The polymer – which hardens within 2 minutes – must be applied to clean skin, with no creams or makeup whatsoever. And makeup cannot be applied over the treated area either, as the area looks irregular and uneven with makeup. This is a very difficult obstacle to overcome for many female patients.

Additionally, to take off the product, the polymer must be dissolved with a special chemical remover that is packaged with the product. Without this key component, it is very difficult and very irritating to remove. Although none of the patients I have used this product on have developed allergic reactions, any synthetic polymer, particularly one with adherent properties, has the potential to be an irritant and/or an allergen. Long-term clinical trials are needed to both validate its efficacy and side-effect profile.

The potential for clinical uses is vast. The product has been shown to provide a synthetic skin barrier that minimizes transepidermal water loss, improving skin hydration. Its uses in burns, atopic dermatitis, bullous disease, and psoriasis could help those with altered skin-barrier function. The researchers are also hoping to use this product for targeted drug delivery and for UV protection.

After a decade of research, the MIT team has developed a skinlike material that is invisible and mimics both the mechanical and elastic properties of the skin. Future clinical studies are essential to evaluating its broad applicability in both dermatology and general medicine.

1. Nature Materials 2016. doi:10.1038/nmat4635.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Dr. Talakoub has no disclosures related to the product. Write to them at [email protected].

Hot off the presses, a new so-called “second skin” is being redeveloped and rebranded for use in both cosmetic and medical dermatology. But what is this substance, and will it hold up to all the claims the manufacturer and research team suggest?

Recently described in Nature Materials, the liquid polymer developed by chemical engineers at MIT is a synthetic, adherent silicone-based film that lies perfectly invisibly on the skin – providing a pulling or temporary tightening of the skin. The product was initially marketed by the company Living Proof as “Neotensil” [an acronym for (Neo) new, (T) transforming, (E) elastic, (N) non-invasive, (S) supportive, (I) invisible, and immediate (L) layer solution]. When applied to the area under the eye, the product creates a so-called “Spanx” effect or tightening of periorbital skin.

The material – called XPL – is delivered in a two-step sequential process. First, a polysiloxane cream is applied to the skin, followed by a platinum catalyst that induces the polymer to harden and tighten the skin underneath. The product uses patented Strateris technology, which is described as creating invisible “shapewear” for the eye; a film that tightens, smooths, and lifts the appearance of skin for up to 24 hours. It was briefly on the market in 2014-2015, then taken off the market to be redeveloped.

Does it work? Yes. Although it takes about an hour to take effect, the clinical results are jaw dropping. However, it also has its drawbacks. The polymer – which hardens within 2 minutes – must be applied to clean skin, with no creams or makeup whatsoever. And makeup cannot be applied over the treated area either, as the area looks irregular and uneven with makeup. This is a very difficult obstacle to overcome for many female patients.

Additionally, to take off the product, the polymer must be dissolved with a special chemical remover that is packaged with the product. Without this key component, it is very difficult and very irritating to remove. Although none of the patients I have used this product on have developed allergic reactions, any synthetic polymer, particularly one with adherent properties, has the potential to be an irritant and/or an allergen. Long-term clinical trials are needed to both validate its efficacy and side-effect profile.

The potential for clinical uses is vast. The product has been shown to provide a synthetic skin barrier that minimizes transepidermal water loss, improving skin hydration. Its uses in burns, atopic dermatitis, bullous disease, and psoriasis could help those with altered skin-barrier function. The researchers are also hoping to use this product for targeted drug delivery and for UV protection.

After a decade of research, the MIT team has developed a skinlike material that is invisible and mimics both the mechanical and elastic properties of the skin. Future clinical studies are essential to evaluating its broad applicability in both dermatology and general medicine.

1. Nature Materials 2016. doi:10.1038/nmat4635.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Dr. Talakoub has no disclosures related to the product. Write to them at [email protected].

LONDON – The European League Against Rheumatism guidelines on the use of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis have been updated in line with current evidence and made more concise.

Dr. Josef S. Smolen of the department of rheumatology at the Medical University of Vienna who presented the 2016 guidelines at the European Congress of Rheumatology, noted that they now consist of 12 rather than the 14 recommendations that were included in the 2013 update (Ann Rheum Dis. 2014;73:492-509) and the 15 recommendations that were in the original 2010 version.

These 12 recommendations cover treatment targets and general approaches in the management of rheumatoid arthritis that incorporate disease-modifying antirheumatic drugs (DMARDs) and the use of glucocorticoids, and present treatment options as a hierarchy to help guide clinicians through appropriate procedures when initial and subsequent treatment fails. All DMARDs are considered in the recommendations, from the long-standing conventional synthetic (cs)DMARDs, such as methotrexate, sulfasalazine, and leflunomide, and the newer biologic DMARDs, such as the anti–tumor necrosis factor (TNF)–targeting drugs, to the newer biosimilar DMARDs, and targeted synthetic (ts)DMARDS, such as the Janus kinase (JAK) inhibitors tofacitinib and baricitinib.

The recommendations have been developed in accordance with EULAR’s standard operating procedure for the development of guidelines, Dr. Smolen observed, and involved three systematic literature reviews and expert opinion garnered from a task force of 50 experts and patients.

“This was the largest task force I have ever convened,” Dr. Smolen said, noting that rheumatologists from outside Europe had been invited to contribute their expertise and knowledge for the first time. Altogether 42 rheumatologists, three clinical fellows, two health professionals, and three patients were involved in revising the recommendations.

There are now four rather than three overarching principles, two of which are shared with early inflammatory arthritis recommendations that were also presented at the congress. The first two principles state that shared decision making is key to optimizing care and that rheumatologists should be the primary specialists looking after patients. The third principle recognizes the high burden that RA can have not only on an individual level but also on health care systems and society in general, which rheumatologists should be aware of. The fourth and final principle states that treatment decisions should be based on patients’ disease activity but that other factors, such as patients’ age, risk for progression, coexisting disease, and likely tolerance of treatment should also be kept in mind.

In an interview, Dr. Smolen highlighted that the EULAR recommendations cover three main phases of DMARD treatment: First is the DMARD-naive group of patients, who may be at an early or late stage of their disease. Second is the group in whom initial treatment has failed, and third is the group for whom subsequent treatment has not worked.

“In all these phases, we have some changes,” Dr. Smolen said. As an example, he noted that in the DMARD-naive setting, the use of csDMARDs has always been recommended but that the prior advice to consider combination csDMARD treatment has been edited out.

“We now say methotrexate should be part of the first treatment strategy, and the treatment strategy encompasses the use of additional, at least conventional synthetic, DMARDs.” Glucocorticoids are also more strongly recommended as part of the initial treatment strategy in combination with methotrexate, he said, although there is the proviso to use these for as short a time as possible.

In situations where patients do not respond to methotrexate plus glucocorticoids or they cannot tolerate methotrexate, then the recommendations advise stratifying patients into two groups. Those with poor prognostic factors might be switched to a biologic therapy, such as an anti-TNF agent or a tsDMARD. In regard to the latter, there is now more evidence behind the use of JAK inhibitors, notably tofacitinib, Dr. Smolen observed. Biologic DMARDs should be combined with csDMARDs, but if the latter is not tolerated then there is the option to use an IL-6 pathway inhibitor.

“There is now compelling evidence that all biologic DMARDs, including tocilizumab, convey better clinical, functional, and structural outcomes in combination with conventional synthetic DMARDs, especially methotrexate,” Dr. Smolen observed during his presentation of the recommendations. This may not be the case for the JAK inhibitors based on the current evidence.

When asked how the EULAR recommendations match up to those issued earlier this year by the American College of Rheumatology (Arthritis Care Res. 2016;68:1-25), Dr. Smolen observed that the two had become “much closer.” There remain differences in recommendations on glucocorticoid use, which are “somewhat clearer” in the European than in the American guidelines, and EULAR proposes combining biologic DMARDs with csDMARDs rather than using them as monotherapy. The EULAR recommendations also do not distinguish patients by disease duration but by treatment phase, and use prognostic factors for stratification.

The recommendations are currently in draft format and once finalized they will be published in Annals of the Rheumatic Diseases and also made freely available via the EULAR website, joining the organization’s many other recommendations for the management of rheumatic diseases. Dr. Smolen noted that these are intended as a template to provide national societies, health systems, and regulatory bodies a guide to the best evidence-based use of DMARDS in RA throughout Europe.

Dr. Smolen has received grant support and/or honoraria for consultations and/or for presentations from: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, ILTOO Pharma, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, and UCB.

LONDON – The European League Against Rheumatism guidelines on the use of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis have been updated in line with current evidence and made more concise.

Dr. Josef S. Smolen of the department of rheumatology at the Medical University of Vienna who presented the 2016 guidelines at the European Congress of Rheumatology, noted that they now consist of 12 rather than the 14 recommendations that were included in the 2013 update (Ann Rheum Dis. 2014;73:492-509) and the 15 recommendations that were in the original 2010 version.

These 12 recommendations cover treatment targets and general approaches in the management of rheumatoid arthritis that incorporate disease-modifying antirheumatic drugs (DMARDs) and the use of glucocorticoids, and present treatment options as a hierarchy to help guide clinicians through appropriate procedures when initial and subsequent treatment fails. All DMARDs are considered in the recommendations, from the long-standing conventional synthetic (cs)DMARDs, such as methotrexate, sulfasalazine, and leflunomide, and the newer biologic DMARDs, such as the anti–tumor necrosis factor (TNF)–targeting drugs, to the newer biosimilar DMARDs, and targeted synthetic (ts)DMARDS, such as the Janus kinase (JAK) inhibitors tofacitinib and baricitinib.

The recommendations have been developed in accordance with EULAR’s standard operating procedure for the development of guidelines, Dr. Smolen observed, and involved three systematic literature reviews and expert opinion garnered from a task force of 50 experts and patients.

“This was the largest task force I have ever convened,” Dr. Smolen said, noting that rheumatologists from outside Europe had been invited to contribute their expertise and knowledge for the first time. Altogether 42 rheumatologists, three clinical fellows, two health professionals, and three patients were involved in revising the recommendations.

There are now four rather than three overarching principles, two of which are shared with early inflammatory arthritis recommendations that were also presented at the congress. The first two principles state that shared decision making is key to optimizing care and that rheumatologists should be the primary specialists looking after patients. The third principle recognizes the high burden that RA can have not only on an individual level but also on health care systems and society in general, which rheumatologists should be aware of. The fourth and final principle states that treatment decisions should be based on patients’ disease activity but that other factors, such as patients’ age, risk for progression, coexisting disease, and likely tolerance of treatment should also be kept in mind.

In an interview, Dr. Smolen highlighted that the EULAR recommendations cover three main phases of DMARD treatment: First is the DMARD-naive group of patients, who may be at an early or late stage of their disease. Second is the group in whom initial treatment has failed, and third is the group for whom subsequent treatment has not worked.

“In all these phases, we have some changes,” Dr. Smolen said. As an example, he noted that in the DMARD-naive setting, the use of csDMARDs has always been recommended but that the prior advice to consider combination csDMARD treatment has been edited out.

“We now say methotrexate should be part of the first treatment strategy, and the treatment strategy encompasses the use of additional, at least conventional synthetic, DMARDs.” Glucocorticoids are also more strongly recommended as part of the initial treatment strategy in combination with methotrexate, he said, although there is the proviso to use these for as short a time as possible.

In situations where patients do not respond to methotrexate plus glucocorticoids or they cannot tolerate methotrexate, then the recommendations advise stratifying patients into two groups. Those with poor prognostic factors might be switched to a biologic therapy, such as an anti-TNF agent or a tsDMARD. In regard to the latter, there is now more evidence behind the use of JAK inhibitors, notably tofacitinib, Dr. Smolen observed. Biologic DMARDs should be combined with csDMARDs, but if the latter is not tolerated then there is the option to use an IL-6 pathway inhibitor.

“There is now compelling evidence that all biologic DMARDs, including tocilizumab, convey better clinical, functional, and structural outcomes in combination with conventional synthetic DMARDs, especially methotrexate,” Dr. Smolen observed during his presentation of the recommendations. This may not be the case for the JAK inhibitors based on the current evidence.

When asked how the EULAR recommendations match up to those issued earlier this year by the American College of Rheumatology (Arthritis Care Res. 2016;68:1-25), Dr. Smolen observed that the two had become “much closer.” There remain differences in recommendations on glucocorticoid use, which are “somewhat clearer” in the European than in the American guidelines, and EULAR proposes combining biologic DMARDs with csDMARDs rather than using them as monotherapy. The EULAR recommendations also do not distinguish patients by disease duration but by treatment phase, and use prognostic factors for stratification.

The recommendations are currently in draft format and once finalized they will be published in Annals of the Rheumatic Diseases and also made freely available via the EULAR website, joining the organization’s many other recommendations for the management of rheumatic diseases. Dr. Smolen noted that these are intended as a template to provide national societies, health systems, and regulatory bodies a guide to the best evidence-based use of DMARDS in RA throughout Europe.

Dr. Smolen has received grant support and/or honoraria for consultations and/or for presentations from: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, ILTOO Pharma, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, and UCB.

LONDON – The European League Against Rheumatism guidelines on the use of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis have been updated in line with current evidence and made more concise.

Dr. Josef S. Smolen of the department of rheumatology at the Medical University of Vienna who presented the 2016 guidelines at the European Congress of Rheumatology, noted that they now consist of 12 rather than the 14 recommendations that were included in the 2013 update (Ann Rheum Dis. 2014;73:492-509) and the 15 recommendations that were in the original 2010 version.

These 12 recommendations cover treatment targets and general approaches in the management of rheumatoid arthritis that incorporate disease-modifying antirheumatic drugs (DMARDs) and the use of glucocorticoids, and present treatment options as a hierarchy to help guide clinicians through appropriate procedures when initial and subsequent treatment fails. All DMARDs are considered in the recommendations, from the long-standing conventional synthetic (cs)DMARDs, such as methotrexate, sulfasalazine, and leflunomide, and the newer biologic DMARDs, such as the anti–tumor necrosis factor (TNF)–targeting drugs, to the newer biosimilar DMARDs, and targeted synthetic (ts)DMARDS, such as the Janus kinase (JAK) inhibitors tofacitinib and baricitinib.

The recommendations have been developed in accordance with EULAR’s standard operating procedure for the development of guidelines, Dr. Smolen observed, and involved three systematic literature reviews and expert opinion garnered from a task force of 50 experts and patients.

“This was the largest task force I have ever convened,” Dr. Smolen said, noting that rheumatologists from outside Europe had been invited to contribute their expertise and knowledge for the first time. Altogether 42 rheumatologists, three clinical fellows, two health professionals, and three patients were involved in revising the recommendations.

There are now four rather than three overarching principles, two of which are shared with early inflammatory arthritis recommendations that were also presented at the congress. The first two principles state that shared decision making is key to optimizing care and that rheumatologists should be the primary specialists looking after patients. The third principle recognizes the high burden that RA can have not only on an individual level but also on health care systems and society in general, which rheumatologists should be aware of. The fourth and final principle states that treatment decisions should be based on patients’ disease activity but that other factors, such as patients’ age, risk for progression, coexisting disease, and likely tolerance of treatment should also be kept in mind.

In an interview, Dr. Smolen highlighted that the EULAR recommendations cover three main phases of DMARD treatment: First is the DMARD-naive group of patients, who may be at an early or late stage of their disease. Second is the group in whom initial treatment has failed, and third is the group for whom subsequent treatment has not worked.

“In all these phases, we have some changes,” Dr. Smolen said. As an example, he noted that in the DMARD-naive setting, the use of csDMARDs has always been recommended but that the prior advice to consider combination csDMARD treatment has been edited out.

“We now say methotrexate should be part of the first treatment strategy, and the treatment strategy encompasses the use of additional, at least conventional synthetic, DMARDs.” Glucocorticoids are also more strongly recommended as part of the initial treatment strategy in combination with methotrexate, he said, although there is the proviso to use these for as short a time as possible.

In situations where patients do not respond to methotrexate plus glucocorticoids or they cannot tolerate methotrexate, then the recommendations advise stratifying patients into two groups. Those with poor prognostic factors might be switched to a biologic therapy, such as an anti-TNF agent or a tsDMARD. In regard to the latter, there is now more evidence behind the use of JAK inhibitors, notably tofacitinib, Dr. Smolen observed. Biologic DMARDs should be combined with csDMARDs, but if the latter is not tolerated then there is the option to use an IL-6 pathway inhibitor.

“There is now compelling evidence that all biologic DMARDs, including tocilizumab, convey better clinical, functional, and structural outcomes in combination with conventional synthetic DMARDs, especially methotrexate,” Dr. Smolen observed during his presentation of the recommendations. This may not be the case for the JAK inhibitors based on the current evidence.

When asked how the EULAR recommendations match up to those issued earlier this year by the American College of Rheumatology (Arthritis Care Res. 2016;68:1-25), Dr. Smolen observed that the two had become “much closer.” There remain differences in recommendations on glucocorticoid use, which are “somewhat clearer” in the European than in the American guidelines, and EULAR proposes combining biologic DMARDs with csDMARDs rather than using them as monotherapy. The EULAR recommendations also do not distinguish patients by disease duration but by treatment phase, and use prognostic factors for stratification.

The recommendations are currently in draft format and once finalized they will be published in Annals of the Rheumatic Diseases and also made freely available via the EULAR website, joining the organization’s many other recommendations for the management of rheumatic diseases. Dr. Smolen noted that these are intended as a template to provide national societies, health systems, and regulatory bodies a guide to the best evidence-based use of DMARDS in RA throughout Europe.

Dr. Smolen has received grant support and/or honoraria for consultations and/or for presentations from: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, ILTOO Pharma, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, and UCB.