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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
New study a reprieve for isoniazid during HIV pregnancy?
SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.
It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.
The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.
The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.
The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).
A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.
As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.
Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.
So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.
“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.
Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm3.
The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.
SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.
SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.
It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.
The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.
The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.
The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).
A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.
As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.
Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.
So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.
“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.
Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm3.
The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.
SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.
SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.
It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.
The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.
The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.
The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).
A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.
As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.
Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.
So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.
“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.
Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm3.
The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.
SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.
REPORTING FROM CROI 2019
For now, HIV cure is worse than infection
SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.
Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.
An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.
He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.
Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.
Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.
Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.
The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.
The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.
The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.
Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.
The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.
He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.
There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.
SOURCE: Gupta RK et al. CROI 2019, Abstract 29.
SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.
Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.
An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.
He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.
Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.
Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.
Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.
The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.
The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.
The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.
Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.
The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.
He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.
There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.
SOURCE: Gupta RK et al. CROI 2019, Abstract 29.
SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.
Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.
An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.
He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.
Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.
Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.
Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.
The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.
The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.
The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.
Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.
The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.
He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.
There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.
SOURCE: Gupta RK et al. CROI 2019, Abstract 29.
REPORTING FROM CROI 2019
Descovy noninferior to Truvada for PrEP
SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection. 
Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.
F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.
The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.
The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.
More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.
There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.
When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.
One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.
For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.
On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m2 in the F/TDF arm, but rose 1.8 mL/min per 1.73 m2 in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.
There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.
In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.
“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”
It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.
The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.
The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.
SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.
SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection.
Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.
F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.
The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.
The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.
More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.
There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.
When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.
One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.
For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.
On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m2 in the F/TDF arm, but rose 1.8 mL/min per 1.73 m2 in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.
There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.
In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.
“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”
It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.
The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.
The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.
SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.
SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection.
Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.
F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.
The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.
The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.
More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.
There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.
When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.
One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.
For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.
On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m2 in the F/TDF arm, but rose 1.8 mL/min per 1.73 m2 in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.
There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.
In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.
“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”
It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.
The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.
The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.
SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.
REPORTING FROM CROI 2019
Opioid overdose risk greater among HIV patients
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
REPORTING FROM CROI 2019
Poor COPD management might increase MI risk in HIV
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
REPORTING FROM CROI 2019
Vagus nerve stimulation for rheumatology? Maybe
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
Point-of-care VL testing improves HIV suppression
SEATTLE – Point-of-care viral load testing improves HIV viral suppression and retention in care, according to a randomized trial of 390 subjects in South Africa.
Point-of-care (POC) testing delivers viral load results in about 2-3 hours, as opposed to the month or so patients wait to get results from a laboratory. The nearly instant turnaround gives clinicians the ability to identify patients who aren’t doing well – as indicated by high viral loads despite antiretroviral therapy (ART) – before they walk out the door, so immediate steps can be taken to address adherence or resistance problems.
However, POC viral load testing hasn’t really caught on in the United States, at least not yet, according to study leader Paul Drain, MD, assistant professor of global health at the University of Washington, Seattle.
To see if it would help, the team turned to a large public clinic in the city of Durban, and focused on adults who had been on ART for 6 months following HIV diagnosis. They randomized 195 to standard laboratory testing at study entrance, with a repeat at 6 months, at which point subjects had been on ART for 12 months; 195 others were randomized to POC testing with the Xpert HIV-1 Viral Load machine, from Cepheid, on the same schedule and with same-day counseling for those with high loads.
Treatment was otherwise similar between the groups, with clinic visits every 2 months and other measures as per South African HIV treatment guidelines.
POC testing made a difference. At study month 12,175 participants (89.7%) in the POC arm, but only 148 (75.9%) in the laboratory testing group, had reached the study’s primary endpoint: viral suppression with less than 200 copies/mL plus retention in care, meaning that subjects were still picking up their ART prescriptions.
Overall, POC testing increased viral load suppression by 10.3%, from 83.1% to 93.3% (P = .003) and retention by 7.7% from 84.6% to 92.3% (P = .03).
The investigators would like to evaluate the approach in the United States. Potentially, “POC testing will have a very important role in U.S. health care,” Dr. Drain said at the Conference on Retroviruses and Opportunistic Infections.
It “helps us identify those who are having problems right away, before they leave the clinic, because whether it’s in South Africa or Seattle, as soon as they leave, it’s very hard to get them back. The more you can do POC testing, the better we can intervene and help these people,” he said.
“You don’t need POC testing for everybody; a lot of people do just fine. They take their medications reliably. They don’t need to get their results back right away ... But there are people who have challenges and would benefit from additional adherence counseling” or who might need help overcoming drug resistance. “We want to identify” them quickly; POC testing may be the answer, he said.
The mean age in the study was 33 years, and 60% of the subjects were women. The median CD4 count at baseline was 468 cells/mm3. POC was $22 per test, versus $25 for lab testing.
The National Institutes of Health funded the work. Dr. Drain had no disclosures. Cepheid donated the POC testing machines.
SOURCE: Drain PK et al. CROI 2019, Abstract 53LB.
SEATTLE – Point-of-care viral load testing improves HIV viral suppression and retention in care, according to a randomized trial of 390 subjects in South Africa.
Point-of-care (POC) testing delivers viral load results in about 2-3 hours, as opposed to the month or so patients wait to get results from a laboratory. The nearly instant turnaround gives clinicians the ability to identify patients who aren’t doing well – as indicated by high viral loads despite antiretroviral therapy (ART) – before they walk out the door, so immediate steps can be taken to address adherence or resistance problems.
However, POC viral load testing hasn’t really caught on in the United States, at least not yet, according to study leader Paul Drain, MD, assistant professor of global health at the University of Washington, Seattle.
To see if it would help, the team turned to a large public clinic in the city of Durban, and focused on adults who had been on ART for 6 months following HIV diagnosis. They randomized 195 to standard laboratory testing at study entrance, with a repeat at 6 months, at which point subjects had been on ART for 12 months; 195 others were randomized to POC testing with the Xpert HIV-1 Viral Load machine, from Cepheid, on the same schedule and with same-day counseling for those with high loads.
Treatment was otherwise similar between the groups, with clinic visits every 2 months and other measures as per South African HIV treatment guidelines.
POC testing made a difference. At study month 12,175 participants (89.7%) in the POC arm, but only 148 (75.9%) in the laboratory testing group, had reached the study’s primary endpoint: viral suppression with less than 200 copies/mL plus retention in care, meaning that subjects were still picking up their ART prescriptions.
Overall, POC testing increased viral load suppression by 10.3%, from 83.1% to 93.3% (P = .003) and retention by 7.7% from 84.6% to 92.3% (P = .03).
The investigators would like to evaluate the approach in the United States. Potentially, “POC testing will have a very important role in U.S. health care,” Dr. Drain said at the Conference on Retroviruses and Opportunistic Infections.
It “helps us identify those who are having problems right away, before they leave the clinic, because whether it’s in South Africa or Seattle, as soon as they leave, it’s very hard to get them back. The more you can do POC testing, the better we can intervene and help these people,” he said.
“You don’t need POC testing for everybody; a lot of people do just fine. They take their medications reliably. They don’t need to get their results back right away ... But there are people who have challenges and would benefit from additional adherence counseling” or who might need help overcoming drug resistance. “We want to identify” them quickly; POC testing may be the answer, he said.
The mean age in the study was 33 years, and 60% of the subjects were women. The median CD4 count at baseline was 468 cells/mm3. POC was $22 per test, versus $25 for lab testing.
The National Institutes of Health funded the work. Dr. Drain had no disclosures. Cepheid donated the POC testing machines.
SOURCE: Drain PK et al. CROI 2019, Abstract 53LB.
SEATTLE – Point-of-care viral load testing improves HIV viral suppression and retention in care, according to a randomized trial of 390 subjects in South Africa.
Point-of-care (POC) testing delivers viral load results in about 2-3 hours, as opposed to the month or so patients wait to get results from a laboratory. The nearly instant turnaround gives clinicians the ability to identify patients who aren’t doing well – as indicated by high viral loads despite antiretroviral therapy (ART) – before they walk out the door, so immediate steps can be taken to address adherence or resistance problems.
However, POC viral load testing hasn’t really caught on in the United States, at least not yet, according to study leader Paul Drain, MD, assistant professor of global health at the University of Washington, Seattle.
To see if it would help, the team turned to a large public clinic in the city of Durban, and focused on adults who had been on ART for 6 months following HIV diagnosis. They randomized 195 to standard laboratory testing at study entrance, with a repeat at 6 months, at which point subjects had been on ART for 12 months; 195 others were randomized to POC testing with the Xpert HIV-1 Viral Load machine, from Cepheid, on the same schedule and with same-day counseling for those with high loads.
Treatment was otherwise similar between the groups, with clinic visits every 2 months and other measures as per South African HIV treatment guidelines.
POC testing made a difference. At study month 12,175 participants (89.7%) in the POC arm, but only 148 (75.9%) in the laboratory testing group, had reached the study’s primary endpoint: viral suppression with less than 200 copies/mL plus retention in care, meaning that subjects were still picking up their ART prescriptions.
Overall, POC testing increased viral load suppression by 10.3%, from 83.1% to 93.3% (P = .003) and retention by 7.7% from 84.6% to 92.3% (P = .03).
The investigators would like to evaluate the approach in the United States. Potentially, “POC testing will have a very important role in U.S. health care,” Dr. Drain said at the Conference on Retroviruses and Opportunistic Infections.
It “helps us identify those who are having problems right away, before they leave the clinic, because whether it’s in South Africa or Seattle, as soon as they leave, it’s very hard to get them back. The more you can do POC testing, the better we can intervene and help these people,” he said.
“You don’t need POC testing for everybody; a lot of people do just fine. They take their medications reliably. They don’t need to get their results back right away ... But there are people who have challenges and would benefit from additional adherence counseling” or who might need help overcoming drug resistance. “We want to identify” them quickly; POC testing may be the answer, he said.
The mean age in the study was 33 years, and 60% of the subjects were women. The median CD4 count at baseline was 468 cells/mm3. POC was $22 per test, versus $25 for lab testing.
The National Institutes of Health funded the work. Dr. Drain had no disclosures. Cepheid donated the POC testing machines.
SOURCE: Drain PK et al. CROI 2019, Abstract 53LB.
REPORTING FROM CROI 2019
TCA and punch excision are two options for icepick acne scars
WAIKOLOA, HAWAII – Dermatologists can certainly improve icepick acne scars, but they have to be careful not to make them worse, according to dermatologist Nazanin Saedi, MD, director of the Jefferson Laser Surgery and Cosmetic Dermatology Center at Thomas Jefferson University, Philadelphia.
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After about three to five TCA treatments, most patients will have a better than 50% improvement, Dr. Saedi said, but the treatment isn’t for darker skin types – Fitzpatrick types V or VI – because of the risk of pigmentation changes. Dr. Saedi uses toothpicks to apply a small amount of 80% TCA to the base of the scar, and waits for the “frost” to appear. It’s important not to reapply the TCA. “A lot of people double dip and ... keep dipping into the scar,” which causes more damage.
For patients with darker skin types, or those who don’t want to go through a series of treatments, punch excision is an option, with nonablative laser treatment a week later when sutures are removed. “Some patients heal beautifully,” but some patients may have a spread scar or a small atrophic scar at the punch site, she noted. Options to treat atrophic scarring after treatment are laser treatments and fillers.
She offered her advice in an interview at the Hawaii Dermatology Seminar, provided by the Global Academy for Medical Education/Skin Disease Education Foundation. It’s important to set realistic expectations, Dr. Saedi said.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Dermatologists can certainly improve icepick acne scars, but they have to be careful not to make them worse, according to dermatologist Nazanin Saedi, MD, director of the Jefferson Laser Surgery and Cosmetic Dermatology Center at Thomas Jefferson University, Philadelphia.
.
After about three to five TCA treatments, most patients will have a better than 50% improvement, Dr. Saedi said, but the treatment isn’t for darker skin types – Fitzpatrick types V or VI – because of the risk of pigmentation changes. Dr. Saedi uses toothpicks to apply a small amount of 80% TCA to the base of the scar, and waits for the “frost” to appear. It’s important not to reapply the TCA. “A lot of people double dip and ... keep dipping into the scar,” which causes more damage.
For patients with darker skin types, or those who don’t want to go through a series of treatments, punch excision is an option, with nonablative laser treatment a week later when sutures are removed. “Some patients heal beautifully,” but some patients may have a spread scar or a small atrophic scar at the punch site, she noted. Options to treat atrophic scarring after treatment are laser treatments and fillers.
She offered her advice in an interview at the Hawaii Dermatology Seminar, provided by the Global Academy for Medical Education/Skin Disease Education Foundation. It’s important to set realistic expectations, Dr. Saedi said.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Dermatologists can certainly improve icepick acne scars, but they have to be careful not to make them worse, according to dermatologist Nazanin Saedi, MD, director of the Jefferson Laser Surgery and Cosmetic Dermatology Center at Thomas Jefferson University, Philadelphia.
.
After about three to five TCA treatments, most patients will have a better than 50% improvement, Dr. Saedi said, but the treatment isn’t for darker skin types – Fitzpatrick types V or VI – because of the risk of pigmentation changes. Dr. Saedi uses toothpicks to apply a small amount of 80% TCA to the base of the scar, and waits for the “frost” to appear. It’s important not to reapply the TCA. “A lot of people double dip and ... keep dipping into the scar,” which causes more damage.
For patients with darker skin types, or those who don’t want to go through a series of treatments, punch excision is an option, with nonablative laser treatment a week later when sutures are removed. “Some patients heal beautifully,” but some patients may have a spread scar or a small atrophic scar at the punch site, she noted. Options to treat atrophic scarring after treatment are laser treatments and fillers.
She offered her advice in an interview at the Hawaii Dermatology Seminar, provided by the Global Academy for Medical Education/Skin Disease Education Foundation. It’s important to set realistic expectations, Dr. Saedi said.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Alisertib response rate in PTCL patients was 33%
An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Simple treatments can address bleeding in dermatologic surgery
WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.
“Part of planning for surgery is to prevent that sort of problem,” and fortunately, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.
During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.
SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.
“Part of planning for surgery is to prevent that sort of problem,” and fortunately, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.
During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.
SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.
“Part of planning for surgery is to prevent that sort of problem,” and fortunately, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.
During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.
SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
