Conference Coverage

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

A version of this article first appeared on Medscape.com.

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

A version of this article first appeared on Medscape.com.

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.

Older adults who have spent time in the intensive care unit have double the risk of developing dementia in later years, compared with older adults who have never stayed in the ICU, new research suggests.

“ICU hospitalization may be an underrecognized risk factor for dementia in older adults,” Bryan D. James, PhD, epidemiologist with Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“Health care providers caring for older patients who have experienced a hospitalization for critical illness should be prepared to assess and monitor their patients’ cognitive status as part of their long-term care plan,” Dr. James added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Hidden risk factor?

ICU hospitalization as a result of critical illness has been linked to subsequent cognitive impairment in older patients. However, how ICU hospitalization relates to the long-term risk of developing Alzheimer’s and other age-related dementias is unknown.

“Given the high rate of ICU hospitalization in older persons, especially during the COVID-19 pandemic, it is critical to explore this relationship, Dr. James said.

The Rush team assessed the impact of an ICU stay on dementia risk in 3,822 older adults (mean age, 77 years) without known dementia at baseline participating in five diverse epidemiologic cohorts.

Participants were checked annually for development of Alzheimer’s and all-type dementia using standardized cognitive assessments.

Over an average of 7.8 years, 1,991 (52%) adults had at least one ICU stay; 1,031 (27%) had an ICU stay before study enrollment; and 961 (25%) had an ICU stay during the study period.

In models adjusted for age, sex, education, and race, ICU hospitalization was associated with 63% higher risk of Alzheimer’s dementia (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) and 71% higher risk of all-type dementia (HR, 1.71; 95% CI, 1.48-1.97).

In models further adjusted for other health factors such as vascular risk factors and disease, other chronic medical conditions and functional disabilities, the association was even stronger: ICU hospitalization was associated with roughly double the risk of Alzheimer’s dementia (HR 2.10; 95% CI, 1.66-2.65) and all-type dementia (HR, 2.20; 95% CI, 1.75-2.77).

Dr. James said in an interview that it remains unclear why an ICU stay may raise the dementia risk.

“This study was not designed to assess the causes of the higher risk of dementia in persons who had ICU hospitalizations. However, researchers have looked into a number of factors that could account for this increased risk,” he explained.

One is critical illness itself that leads to hospitalization, which could result in damage to the brain; for example, severe COVID-19 has been shown to directly harm the brain, Dr. James said.

He also noted that specific events experienced during ICU stay have been shown to increase risk for cognitive impairment, including infection and severe sepsis, acute dialysis, neurologic dysfunction and delirium, and sedation.
 

Important work

Commenting on the study, Heather Snyder, PhD, vice president of medical & scientific relations at the Alzheimer’s Association, said what’s interesting about the study is that it looks at individuals in the ICU, regardless of the cause.

“The study shows that having some type of health issue that results in some type of ICU stay is associated with an increased risk of declining cognition,” Dr. Snyder said.

“That’s really important,” she said, “especially given the increase in individuals, particularly those 60 and older, who did experience an ICU stay over the last couple of years and understanding how that might impact their long-term risk related to Alzheimer’s and other changes in memory.”

“If an individual has been in the ICU, that should be part of the conversation with their physician or health care provider,” Dr. Snyder advised.

The study was funded by the National Institute on Aging. Dr. James and Dr. Snyder disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Older adults who have spent time in the intensive care unit have double the risk of developing dementia in later years, compared with older adults who have never stayed in the ICU, new research suggests.

“ICU hospitalization may be an underrecognized risk factor for dementia in older adults,” Bryan D. James, PhD, epidemiologist with Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“Health care providers caring for older patients who have experienced a hospitalization for critical illness should be prepared to assess and monitor their patients’ cognitive status as part of their long-term care plan,” Dr. James added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Hidden risk factor?

ICU hospitalization as a result of critical illness has been linked to subsequent cognitive impairment in older patients. However, how ICU hospitalization relates to the long-term risk of developing Alzheimer’s and other age-related dementias is unknown.

“Given the high rate of ICU hospitalization in older persons, especially during the COVID-19 pandemic, it is critical to explore this relationship, Dr. James said.

The Rush team assessed the impact of an ICU stay on dementia risk in 3,822 older adults (mean age, 77 years) without known dementia at baseline participating in five diverse epidemiologic cohorts.

Participants were checked annually for development of Alzheimer’s and all-type dementia using standardized cognitive assessments.

Over an average of 7.8 years, 1,991 (52%) adults had at least one ICU stay; 1,031 (27%) had an ICU stay before study enrollment; and 961 (25%) had an ICU stay during the study period.

In models adjusted for age, sex, education, and race, ICU hospitalization was associated with 63% higher risk of Alzheimer’s dementia (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) and 71% higher risk of all-type dementia (HR, 1.71; 95% CI, 1.48-1.97).

In models further adjusted for other health factors such as vascular risk factors and disease, other chronic medical conditions and functional disabilities, the association was even stronger: ICU hospitalization was associated with roughly double the risk of Alzheimer’s dementia (HR 2.10; 95% CI, 1.66-2.65) and all-type dementia (HR, 2.20; 95% CI, 1.75-2.77).

Dr. James said in an interview that it remains unclear why an ICU stay may raise the dementia risk.

“This study was not designed to assess the causes of the higher risk of dementia in persons who had ICU hospitalizations. However, researchers have looked into a number of factors that could account for this increased risk,” he explained.

One is critical illness itself that leads to hospitalization, which could result in damage to the brain; for example, severe COVID-19 has been shown to directly harm the brain, Dr. James said.

He also noted that specific events experienced during ICU stay have been shown to increase risk for cognitive impairment, including infection and severe sepsis, acute dialysis, neurologic dysfunction and delirium, and sedation.
 

Important work

Commenting on the study, Heather Snyder, PhD, vice president of medical & scientific relations at the Alzheimer’s Association, said what’s interesting about the study is that it looks at individuals in the ICU, regardless of the cause.

“The study shows that having some type of health issue that results in some type of ICU stay is associated with an increased risk of declining cognition,” Dr. Snyder said.

“That’s really important,” she said, “especially given the increase in individuals, particularly those 60 and older, who did experience an ICU stay over the last couple of years and understanding how that might impact their long-term risk related to Alzheimer’s and other changes in memory.”

“If an individual has been in the ICU, that should be part of the conversation with their physician or health care provider,” Dr. Snyder advised.

The study was funded by the National Institute on Aging. Dr. James and Dr. Snyder disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Older adults who have spent time in the intensive care unit have double the risk of developing dementia in later years, compared with older adults who have never stayed in the ICU, new research suggests.

“ICU hospitalization may be an underrecognized risk factor for dementia in older adults,” Bryan D. James, PhD, epidemiologist with Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“Health care providers caring for older patients who have experienced a hospitalization for critical illness should be prepared to assess and monitor their patients’ cognitive status as part of their long-term care plan,” Dr. James added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Hidden risk factor?

ICU hospitalization as a result of critical illness has been linked to subsequent cognitive impairment in older patients. However, how ICU hospitalization relates to the long-term risk of developing Alzheimer’s and other age-related dementias is unknown.

“Given the high rate of ICU hospitalization in older persons, especially during the COVID-19 pandemic, it is critical to explore this relationship, Dr. James said.

The Rush team assessed the impact of an ICU stay on dementia risk in 3,822 older adults (mean age, 77 years) without known dementia at baseline participating in five diverse epidemiologic cohorts.

Participants were checked annually for development of Alzheimer’s and all-type dementia using standardized cognitive assessments.

Over an average of 7.8 years, 1,991 (52%) adults had at least one ICU stay; 1,031 (27%) had an ICU stay before study enrollment; and 961 (25%) had an ICU stay during the study period.

In models adjusted for age, sex, education, and race, ICU hospitalization was associated with 63% higher risk of Alzheimer’s dementia (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) and 71% higher risk of all-type dementia (HR, 1.71; 95% CI, 1.48-1.97).

In models further adjusted for other health factors such as vascular risk factors and disease, other chronic medical conditions and functional disabilities, the association was even stronger: ICU hospitalization was associated with roughly double the risk of Alzheimer’s dementia (HR 2.10; 95% CI, 1.66-2.65) and all-type dementia (HR, 2.20; 95% CI, 1.75-2.77).

Dr. James said in an interview that it remains unclear why an ICU stay may raise the dementia risk.

“This study was not designed to assess the causes of the higher risk of dementia in persons who had ICU hospitalizations. However, researchers have looked into a number of factors that could account for this increased risk,” he explained.

One is critical illness itself that leads to hospitalization, which could result in damage to the brain; for example, severe COVID-19 has been shown to directly harm the brain, Dr. James said.

He also noted that specific events experienced during ICU stay have been shown to increase risk for cognitive impairment, including infection and severe sepsis, acute dialysis, neurologic dysfunction and delirium, and sedation.
 

Important work

Commenting on the study, Heather Snyder, PhD, vice president of medical & scientific relations at the Alzheimer’s Association, said what’s interesting about the study is that it looks at individuals in the ICU, regardless of the cause.

“The study shows that having some type of health issue that results in some type of ICU stay is associated with an increased risk of declining cognition,” Dr. Snyder said.

“That’s really important,” she said, “especially given the increase in individuals, particularly those 60 and older, who did experience an ICU stay over the last couple of years and understanding how that might impact their long-term risk related to Alzheimer’s and other changes in memory.”

“If an individual has been in the ICU, that should be part of the conversation with their physician or health care provider,” Dr. Snyder advised.

The study was funded by the National Institute on Aging. Dr. James and Dr. Snyder disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that food allergies in children and adolescents are grossly overdiagnosed and misdiagnosed.

“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.

During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.

While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”

Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.

Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”

Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.

“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.

The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”

Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.

“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”

IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.

“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).

With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.

“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”

He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”

Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?

“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.

According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.

“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”

Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.

INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that food allergies in children and adolescents are grossly overdiagnosed and misdiagnosed.

“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.

During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.

While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”

Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.

Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”

Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.

“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.

The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”

Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.

“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”

IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.

“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).

With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.

“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”

He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”

Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?

“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.

According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.

“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”

Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.

INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that food allergies in children and adolescents are grossly overdiagnosed and misdiagnosed.

“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.

During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.

While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”

Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.

Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”

Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.

“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.

The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”

Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.

“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”

IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.

“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).

With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.

“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”

He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”

Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?

“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.

According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.

“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”

Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.

From crow’s feet to sagging nasolabial folds to prominent platysmal bands, many patients want to erase some years from their faces, and many want to do so without invasive procedures.

At the MedscapeLive’s Women’s and Pediatric Dermatology Seminar, Jacqueline Watchmaker, MD, a dermatologist in Scottsdale, Ariz., provided an overview of current options, along with advice on how to keep patients’ expectations realistic and how to properly choose the best candidates for the best procedures.

“One of the most common concerns patients come to me with are wrinkles on the upper face,” but this is far from their only concern, Dr. Watchmaker said. Wrinkles and sagging of the lower face, areas under the eyes, nasolabial folds, marionette lines, and the neck also draw concern. Uneven coloration is another common concern, she said.

“So, what can we do for all of this?” she asked. The options are plentiful. Wrinkles of the upper face are easy to address with neuromodulators, she said, and soft-tissue fillers help the jawline and cheek areas.

“For the lower face, skin tightening devices really shine,” she added. And lasers can help correct uneven coloration. Surgery, of course, can also produce good results, but many patients want to stick with noninvasive or minimally invasive procedures.
 

Case: 83-year-old woman

Dr. Watchmaker discussed an 83-year old patient, who had malar mounds and accentuation of the infraorbital hollowness resulting from changes in subcutaneous fat and ligament laxity. She also had uneven coloration from photo damage, wrinkles on the upper face, linear appearance of zygoma related to underlying bony changes and fat compartment descent, and nasolabial folds and jowls related to decreased bony compartments, ligament laxity, and shifting of fat. She was naive to any cosmetic procedure.

Despite her age, this patient had no wrinkling on the upper forehead. Dr. Watchmaker did not inject neuromodulator in the upper forehead, as this patient also had a slightly heavy eyelid. “If you inject too much, it can cause some drooping of the eyelid and eyebrow,” she said.

For filler, she used a combination of high G (firmness, support) hyaluronic acid filler, a medium G acid filler, and a low G filler. The result: The woman’s face became more balanced, the mid-face volumization lifted the lower face, and the glabellar and periocular lines were softer, although still present. “It’s important to counsel patients that neuromodulators won’t make the lines go away the first time, but they will be softened.”
 

Practice tips

It’s important to titrate neuromodulators to fit the patient, Dr. Watchmaker said. Ask: What are their goals: Reversal of static lines? Softening wrinkles? Maintaining current status? “There’s not one dosing regimen,” and both dosing and frequency of neuromodulators can be titrated to fit each patient’s aesthetic goals, she said. For older patients who want to soften or maintain appearance, she suggested treatment every 4-6 months. And some patients just want to maintain the status quo, she noted.

Ideal candidates

For neuromodulators and fillers, who is an ideal candidate? “I think it’s anyone who has realistic expectations,” she said. Patients need to know how many treatments are needed and how much it will cost. For patients with extensive wrinkling and sagging, she said, she does extensive counseling about what results to expect “because I don’t want them to feel like they wasted their time or their money.”

She also suggests a surgical consult, as some may opt for that route after learning about the options and expected results.
 

Skin tightening

Both radiofrequency and microfocused ultrasound are noninvasive and additional options. Radiofrequency uses radio waves, with electromagnetic energy to stimulate heat. Ultrasound uses ultrasound waves to stimulate heat. Both approaches cause collagen contraction, neocollagenesis, and skin tightening.

These procedures do well for the lower face, Dr. Watchmaker said, but “I am relatively unimpressed for how well they do for the upper face.” Ideal candidates have mild to moderate skin laxity and want to avoid surgery. She also tells patients that collagen isn’t made overnight. “You won’t see much for 3-6 months after.” The good news? Usually the treatments need to be repeated only every 1.5-2 years, she said.
 

Lasers

“There are so many lasers out there,” said Dr. Watchmaker, who groups them into three categories: those used for wrinkles, dyschromia, and erythema. Her picks: ablative lasers (CO² and erbium) and erbium-doped YAG 1550 nm laser for rhytids. Thulium 1927 and QS and picosecond lasers are her picks for dyschromia, and for erythema, pulsed dye and KTP lasers.

Some laser treatments are not a “walk in the park,” as she warns patients. For example, after treatment with ablative lasers, there is pain, post-procedure redness, and crusting.
 

Take-home points

A combination of noninvasive and minimally invasive procedures can produce appearance-improving results. That’s more likely if dermatologists choose ideal candidates, personalize the treatment, and set realistic expectations. “We have a finite number of tools,” she said, but they can be used in a variety of ways.

At the interactive panel discussion following her presentation, Dr. Watchmaker was asked what she tells patients about sun protection. “I talk a lot about sunscreens,’’ she said, always urging patients to use them. While the options for rejuvenation are numerous, taking care of the skin is still crucial.

Dr. Watchmaker had no disclosures. MedscapeLive and this news organization are owned by the same parent company.

From crow’s feet to sagging nasolabial folds to prominent platysmal bands, many patients want to erase some years from their faces, and many want to do so without invasive procedures.

At the MedscapeLive’s Women’s and Pediatric Dermatology Seminar, Jacqueline Watchmaker, MD, a dermatologist in Scottsdale, Ariz., provided an overview of current options, along with advice on how to keep patients’ expectations realistic and how to properly choose the best candidates for the best procedures.

“One of the most common concerns patients come to me with are wrinkles on the upper face,” but this is far from their only concern, Dr. Watchmaker said. Wrinkles and sagging of the lower face, areas under the eyes, nasolabial folds, marionette lines, and the neck also draw concern. Uneven coloration is another common concern, she said.

“So, what can we do for all of this?” she asked. The options are plentiful. Wrinkles of the upper face are easy to address with neuromodulators, she said, and soft-tissue fillers help the jawline and cheek areas.

“For the lower face, skin tightening devices really shine,” she added. And lasers can help correct uneven coloration. Surgery, of course, can also produce good results, but many patients want to stick with noninvasive or minimally invasive procedures.
 

Case: 83-year-old woman

Dr. Watchmaker discussed an 83-year old patient, who had malar mounds and accentuation of the infraorbital hollowness resulting from changes in subcutaneous fat and ligament laxity. She also had uneven coloration from photo damage, wrinkles on the upper face, linear appearance of zygoma related to underlying bony changes and fat compartment descent, and nasolabial folds and jowls related to decreased bony compartments, ligament laxity, and shifting of fat. She was naive to any cosmetic procedure.

Despite her age, this patient had no wrinkling on the upper forehead. Dr. Watchmaker did not inject neuromodulator in the upper forehead, as this patient also had a slightly heavy eyelid. “If you inject too much, it can cause some drooping of the eyelid and eyebrow,” she said.

For filler, she used a combination of high G (firmness, support) hyaluronic acid filler, a medium G acid filler, and a low G filler. The result: The woman’s face became more balanced, the mid-face volumization lifted the lower face, and the glabellar and periocular lines were softer, although still present. “It’s important to counsel patients that neuromodulators won’t make the lines go away the first time, but they will be softened.”
 

Practice tips

It’s important to titrate neuromodulators to fit the patient, Dr. Watchmaker said. Ask: What are their goals: Reversal of static lines? Softening wrinkles? Maintaining current status? “There’s not one dosing regimen,” and both dosing and frequency of neuromodulators can be titrated to fit each patient’s aesthetic goals, she said. For older patients who want to soften or maintain appearance, she suggested treatment every 4-6 months. And some patients just want to maintain the status quo, she noted.

Ideal candidates

For neuromodulators and fillers, who is an ideal candidate? “I think it’s anyone who has realistic expectations,” she said. Patients need to know how many treatments are needed and how much it will cost. For patients with extensive wrinkling and sagging, she said, she does extensive counseling about what results to expect “because I don’t want them to feel like they wasted their time or their money.”

She also suggests a surgical consult, as some may opt for that route after learning about the options and expected results.
 

Skin tightening

Both radiofrequency and microfocused ultrasound are noninvasive and additional options. Radiofrequency uses radio waves, with electromagnetic energy to stimulate heat. Ultrasound uses ultrasound waves to stimulate heat. Both approaches cause collagen contraction, neocollagenesis, and skin tightening.

These procedures do well for the lower face, Dr. Watchmaker said, but “I am relatively unimpressed for how well they do for the upper face.” Ideal candidates have mild to moderate skin laxity and want to avoid surgery. She also tells patients that collagen isn’t made overnight. “You won’t see much for 3-6 months after.” The good news? Usually the treatments need to be repeated only every 1.5-2 years, she said.
 

Lasers

“There are so many lasers out there,” said Dr. Watchmaker, who groups them into three categories: those used for wrinkles, dyschromia, and erythema. Her picks: ablative lasers (CO² and erbium) and erbium-doped YAG 1550 nm laser for rhytids. Thulium 1927 and QS and picosecond lasers are her picks for dyschromia, and for erythema, pulsed dye and KTP lasers.

Some laser treatments are not a “walk in the park,” as she warns patients. For example, after treatment with ablative lasers, there is pain, post-procedure redness, and crusting.
 

Take-home points

A combination of noninvasive and minimally invasive procedures can produce appearance-improving results. That’s more likely if dermatologists choose ideal candidates, personalize the treatment, and set realistic expectations. “We have a finite number of tools,” she said, but they can be used in a variety of ways.

At the interactive panel discussion following her presentation, Dr. Watchmaker was asked what she tells patients about sun protection. “I talk a lot about sunscreens,’’ she said, always urging patients to use them. While the options for rejuvenation are numerous, taking care of the skin is still crucial.

Dr. Watchmaker had no disclosures. MedscapeLive and this news organization are owned by the same parent company.

From crow’s feet to sagging nasolabial folds to prominent platysmal bands, many patients want to erase some years from their faces, and many want to do so without invasive procedures.

At the MedscapeLive’s Women’s and Pediatric Dermatology Seminar, Jacqueline Watchmaker, MD, a dermatologist in Scottsdale, Ariz., provided an overview of current options, along with advice on how to keep patients’ expectations realistic and how to properly choose the best candidates for the best procedures.

“One of the most common concerns patients come to me with are wrinkles on the upper face,” but this is far from their only concern, Dr. Watchmaker said. Wrinkles and sagging of the lower face, areas under the eyes, nasolabial folds, marionette lines, and the neck also draw concern. Uneven coloration is another common concern, she said.

“So, what can we do for all of this?” she asked. The options are plentiful. Wrinkles of the upper face are easy to address with neuromodulators, she said, and soft-tissue fillers help the jawline and cheek areas.

“For the lower face, skin tightening devices really shine,” she added. And lasers can help correct uneven coloration. Surgery, of course, can also produce good results, but many patients want to stick with noninvasive or minimally invasive procedures.
 

Case: 83-year-old woman

Dr. Watchmaker discussed an 83-year old patient, who had malar mounds and accentuation of the infraorbital hollowness resulting from changes in subcutaneous fat and ligament laxity. She also had uneven coloration from photo damage, wrinkles on the upper face, linear appearance of zygoma related to underlying bony changes and fat compartment descent, and nasolabial folds and jowls related to decreased bony compartments, ligament laxity, and shifting of fat. She was naive to any cosmetic procedure.

Despite her age, this patient had no wrinkling on the upper forehead. Dr. Watchmaker did not inject neuromodulator in the upper forehead, as this patient also had a slightly heavy eyelid. “If you inject too much, it can cause some drooping of the eyelid and eyebrow,” she said.

For filler, she used a combination of high G (firmness, support) hyaluronic acid filler, a medium G acid filler, and a low G filler. The result: The woman’s face became more balanced, the mid-face volumization lifted the lower face, and the glabellar and periocular lines were softer, although still present. “It’s important to counsel patients that neuromodulators won’t make the lines go away the first time, but they will be softened.”
 

Practice tips

It’s important to titrate neuromodulators to fit the patient, Dr. Watchmaker said. Ask: What are their goals: Reversal of static lines? Softening wrinkles? Maintaining current status? “There’s not one dosing regimen,” and both dosing and frequency of neuromodulators can be titrated to fit each patient’s aesthetic goals, she said. For older patients who want to soften or maintain appearance, she suggested treatment every 4-6 months. And some patients just want to maintain the status quo, she noted.

Ideal candidates

For neuromodulators and fillers, who is an ideal candidate? “I think it’s anyone who has realistic expectations,” she said. Patients need to know how many treatments are needed and how much it will cost. For patients with extensive wrinkling and sagging, she said, she does extensive counseling about what results to expect “because I don’t want them to feel like they wasted their time or their money.”

She also suggests a surgical consult, as some may opt for that route after learning about the options and expected results.
 

Skin tightening

Both radiofrequency and microfocused ultrasound are noninvasive and additional options. Radiofrequency uses radio waves, with electromagnetic energy to stimulate heat. Ultrasound uses ultrasound waves to stimulate heat. Both approaches cause collagen contraction, neocollagenesis, and skin tightening.

These procedures do well for the lower face, Dr. Watchmaker said, but “I am relatively unimpressed for how well they do for the upper face.” Ideal candidates have mild to moderate skin laxity and want to avoid surgery. She also tells patients that collagen isn’t made overnight. “You won’t see much for 3-6 months after.” The good news? Usually the treatments need to be repeated only every 1.5-2 years, she said.
 

Lasers

“There are so many lasers out there,” said Dr. Watchmaker, who groups them into three categories: those used for wrinkles, dyschromia, and erythema. Her picks: ablative lasers (CO² and erbium) and erbium-doped YAG 1550 nm laser for rhytids. Thulium 1927 and QS and picosecond lasers are her picks for dyschromia, and for erythema, pulsed dye and KTP lasers.

Some laser treatments are not a “walk in the park,” as she warns patients. For example, after treatment with ablative lasers, there is pain, post-procedure redness, and crusting.
 

Take-home points

A combination of noninvasive and minimally invasive procedures can produce appearance-improving results. That’s more likely if dermatologists choose ideal candidates, personalize the treatment, and set realistic expectations. “We have a finite number of tools,” she said, but they can be used in a variety of ways.

At the interactive panel discussion following her presentation, Dr. Watchmaker was asked what she tells patients about sun protection. “I talk a lot about sunscreens,’’ she said, always urging patients to use them. While the options for rejuvenation are numerous, taking care of the skin is still crucial.

Dr. Watchmaker had no disclosures. MedscapeLive and this news organization are owned by the same parent company.

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.