Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Last night I invested an hour and a half watching the first half of the Super Bowl ... because ... well, just because. As exciting as it might have been to watch, investing another 2 hours on the second half would have kept me up well past my bedtime. As I lay in bed with the thwack-thwack-thud of helmets hitting pads still reverberating in my ears, my thoughts drifted to the ever-shifting landscape of concussion management.

More than 2 decades ago, concussions were just beginning to exit the dark ages when loss of consciousness was the defining symptom or sign that most folks (and here I am including physicians) used to separate the run-of-the-mill stinger or bell-ringer from a “real” concussion.

The new era dawned with the appearance of clinics devoted to concussion management and the development of protocols that limited everything from physical exertion to reading and screen time. Schools were coaxed into subjecting their athletes to preparticipation testing sessions with the hope that creating a baseline cognitive assessment would somehow make the diagnosis and management of concussion feel more scientific. Many of the recommended management strategies were based on the intuitive but flawed notion of “brain rest.” If reading or bright lights aggravate patient’s symptoms, they should be avoided but otherwise resting the brain doesn’t seem to make sense.

Fortunately, there were, and hopefully will continue to be, clinicians willing to question hastily developed management protocols. One recent cohort study from Canada has found that, surprisingly, (to some experts), “early return to school was associated with a lower symptom burden” This association held true for both age groups the researches studied (8-12 years and 13-18 years). The authors conclude that delayed return to school “may be detrimental to recovery.” In this study, early return to school was defined as less than 3 days.

In another study, this one in the journal Pediatrics, the authors found that “the association of early screen time with postconcussion symptoms is not linear.” Their conclusion was that the best approach to clinical management of concussion should include a moderate amount of screen time.

After reading both of these studies I am heartened that we are now hearing voices suggesting a return to concussion management based on careful observation of the individual patient and common sense. A concussed brain is not a torn hamstring or a broken clavicle that under most circumstances will heal in a predictable amount of time. It is prudent to exclude the concussed patient from activities that carry a significant risk of reinjury until the symptoms have subsided. However, postconcussion symptoms are often vague and can be mistaken for or aggravated by a host of other conditions including learning disabilities, anxiety, and depression.

I hope that our experience with the COVID pandemic has taught us that removing children from school and their usual activities can have a serious negative effect on their emotional health and academic achievement. This seems to be particularly true for the young people who were already struggling to adjust to being a student. Getting out of the habit of going to school often intensifies the anxieties of an emotionally or academically challenged student. Each day away from the school atmosphere can compound the symptoms that may or may not have been triggered by the concussion.

The message here is clear that, whether we are talking about concussions or appendectomies or mononucleosis, the sooner we can return the child to something close to their old normal the more successful we will be in a helping them adjust to the new normal.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Last night I invested an hour and a half watching the first half of the Super Bowl ... because ... well, just because. As exciting as it might have been to watch, investing another 2 hours on the second half would have kept me up well past my bedtime. As I lay in bed with the thwack-thwack-thud of helmets hitting pads still reverberating in my ears, my thoughts drifted to the ever-shifting landscape of concussion management.

More than 2 decades ago, concussions were just beginning to exit the dark ages when loss of consciousness was the defining symptom or sign that most folks (and here I am including physicians) used to separate the run-of-the-mill stinger or bell-ringer from a “real” concussion.

The new era dawned with the appearance of clinics devoted to concussion management and the development of protocols that limited everything from physical exertion to reading and screen time. Schools were coaxed into subjecting their athletes to preparticipation testing sessions with the hope that creating a baseline cognitive assessment would somehow make the diagnosis and management of concussion feel more scientific. Many of the recommended management strategies were based on the intuitive but flawed notion of “brain rest.” If reading or bright lights aggravate patient’s symptoms, they should be avoided but otherwise resting the brain doesn’t seem to make sense.

Fortunately, there were, and hopefully will continue to be, clinicians willing to question hastily developed management protocols. One recent cohort study from Canada has found that, surprisingly, (to some experts), “early return to school was associated with a lower symptom burden” This association held true for both age groups the researches studied (8-12 years and 13-18 years). The authors conclude that delayed return to school “may be detrimental to recovery.” In this study, early return to school was defined as less than 3 days.

In another study, this one in the journal Pediatrics, the authors found that “the association of early screen time with postconcussion symptoms is not linear.” Their conclusion was that the best approach to clinical management of concussion should include a moderate amount of screen time.

After reading both of these studies I am heartened that we are now hearing voices suggesting a return to concussion management based on careful observation of the individual patient and common sense. A concussed brain is not a torn hamstring or a broken clavicle that under most circumstances will heal in a predictable amount of time. It is prudent to exclude the concussed patient from activities that carry a significant risk of reinjury until the symptoms have subsided. However, postconcussion symptoms are often vague and can be mistaken for or aggravated by a host of other conditions including learning disabilities, anxiety, and depression.

I hope that our experience with the COVID pandemic has taught us that removing children from school and their usual activities can have a serious negative effect on their emotional health and academic achievement. This seems to be particularly true for the young people who were already struggling to adjust to being a student. Getting out of the habit of going to school often intensifies the anxieties of an emotionally or academically challenged student. Each day away from the school atmosphere can compound the symptoms that may or may not have been triggered by the concussion.

The message here is clear that, whether we are talking about concussions or appendectomies or mononucleosis, the sooner we can return the child to something close to their old normal the more successful we will be in a helping them adjust to the new normal.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Last night I invested an hour and a half watching the first half of the Super Bowl ... because ... well, just because. As exciting as it might have been to watch, investing another 2 hours on the second half would have kept me up well past my bedtime. As I lay in bed with the thwack-thwack-thud of helmets hitting pads still reverberating in my ears, my thoughts drifted to the ever-shifting landscape of concussion management.

More than 2 decades ago, concussions were just beginning to exit the dark ages when loss of consciousness was the defining symptom or sign that most folks (and here I am including physicians) used to separate the run-of-the-mill stinger or bell-ringer from a “real” concussion.

The new era dawned with the appearance of clinics devoted to concussion management and the development of protocols that limited everything from physical exertion to reading and screen time. Schools were coaxed into subjecting their athletes to preparticipation testing sessions with the hope that creating a baseline cognitive assessment would somehow make the diagnosis and management of concussion feel more scientific. Many of the recommended management strategies were based on the intuitive but flawed notion of “brain rest.” If reading or bright lights aggravate patient’s symptoms, they should be avoided but otherwise resting the brain doesn’t seem to make sense.

Fortunately, there were, and hopefully will continue to be, clinicians willing to question hastily developed management protocols. One recent cohort study from Canada has found that, surprisingly, (to some experts), “early return to school was associated with a lower symptom burden” This association held true for both age groups the researches studied (8-12 years and 13-18 years). The authors conclude that delayed return to school “may be detrimental to recovery.” In this study, early return to school was defined as less than 3 days.

In another study, this one in the journal Pediatrics, the authors found that “the association of early screen time with postconcussion symptoms is not linear.” Their conclusion was that the best approach to clinical management of concussion should include a moderate amount of screen time.

After reading both of these studies I am heartened that we are now hearing voices suggesting a return to concussion management based on careful observation of the individual patient and common sense. A concussed brain is not a torn hamstring or a broken clavicle that under most circumstances will heal in a predictable amount of time. It is prudent to exclude the concussed patient from activities that carry a significant risk of reinjury until the symptoms have subsided. However, postconcussion symptoms are often vague and can be mistaken for or aggravated by a host of other conditions including learning disabilities, anxiety, and depression.

I hope that our experience with the COVID pandemic has taught us that removing children from school and their usual activities can have a serious negative effect on their emotional health and academic achievement. This seems to be particularly true for the young people who were already struggling to adjust to being a student. Getting out of the habit of going to school often intensifies the anxieties of an emotionally or academically challenged student. Each day away from the school atmosphere can compound the symptoms that may or may not have been triggered by the concussion.

The message here is clear that, whether we are talking about concussions or appendectomies or mononucleosis, the sooner we can return the child to something close to their old normal the more successful we will be in a helping them adjust to the new normal.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The Food and Drug Administration has approved efanesoctocog alfa (Altuviiio), a first-in-class, high-sustained factor VIII replacement therapy for adults and children with hemophilia A.

The product is used once a week and is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as to control bleeding during surgery (perioperative management).

The manufacturer, Sanofi, says that this is “the first and only hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis.”

With this product, “we have the opportunity to provide near-normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” said Angela Weyand, MD, of Michigan Medicine, who was involved in the pivotal phase 3 XTEND-1 trial that led to approval.

Results from the XTEND-1 trial were recently published online in The New England Journal of Medicine. The results show that one injection of efanesoctocog alfa, a factor VIII therapy, resolved almost all bleeding episodes (97%) in the overall patient population and weekly prophylaxis provided mean factor VIII activity in the normal or near-normal range (> 40 IU/dL) for most of the week, as previously reported by this news organization.

The researchers noted that the factor VIII therapies that have been available up to now need to be administered frequently.

In an accompanying editorial, Cindy Leissinger, MD, called efanesoctocog alfa a “victory” for patients with hemophilia A.

“In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner – a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion,” wrote Dr. Leissinger, director of the Louisiana Center for Bleeding and Clotting Disorders at Tulane University in New Orleans.

Sanofi said that Altuviiio is expected to be commercially available in April 2023. The company said that it will price the product at parity to the annual cost of treating a prophylaxis patient with its Eloctate product (antihemophilic factor [recombinant], Fc fusion protein). Sanofi will provide comprehensive patient support services and resources online and at 1-855-MyALTUVIIIO (855-692-5888).

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

The Food and Drug Administration has approved efanesoctocog alfa (Altuviiio), a first-in-class, high-sustained factor VIII replacement therapy for adults and children with hemophilia A.

The product is used once a week and is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as to control bleeding during surgery (perioperative management).

The manufacturer, Sanofi, says that this is “the first and only hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis.”

With this product, “we have the opportunity to provide near-normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” said Angela Weyand, MD, of Michigan Medicine, who was involved in the pivotal phase 3 XTEND-1 trial that led to approval.

Results from the XTEND-1 trial were recently published online in The New England Journal of Medicine. The results show that one injection of efanesoctocog alfa, a factor VIII therapy, resolved almost all bleeding episodes (97%) in the overall patient population and weekly prophylaxis provided mean factor VIII activity in the normal or near-normal range (> 40 IU/dL) for most of the week, as previously reported by this news organization.

The researchers noted that the factor VIII therapies that have been available up to now need to be administered frequently.

In an accompanying editorial, Cindy Leissinger, MD, called efanesoctocog alfa a “victory” for patients with hemophilia A.

“In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner – a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion,” wrote Dr. Leissinger, director of the Louisiana Center for Bleeding and Clotting Disorders at Tulane University in New Orleans.

Sanofi said that Altuviiio is expected to be commercially available in April 2023. The company said that it will price the product at parity to the annual cost of treating a prophylaxis patient with its Eloctate product (antihemophilic factor [recombinant], Fc fusion protein). Sanofi will provide comprehensive patient support services and resources online and at 1-855-MyALTUVIIIO (855-692-5888).

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

The Food and Drug Administration has approved efanesoctocog alfa (Altuviiio), a first-in-class, high-sustained factor VIII replacement therapy for adults and children with hemophilia A.

The product is used once a week and is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as to control bleeding during surgery (perioperative management).

The manufacturer, Sanofi, says that this is “the first and only hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis.”

With this product, “we have the opportunity to provide near-normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” said Angela Weyand, MD, of Michigan Medicine, who was involved in the pivotal phase 3 XTEND-1 trial that led to approval.

Results from the XTEND-1 trial were recently published online in The New England Journal of Medicine. The results show that one injection of efanesoctocog alfa, a factor VIII therapy, resolved almost all bleeding episodes (97%) in the overall patient population and weekly prophylaxis provided mean factor VIII activity in the normal or near-normal range (> 40 IU/dL) for most of the week, as previously reported by this news organization.

The researchers noted that the factor VIII therapies that have been available up to now need to be administered frequently.

In an accompanying editorial, Cindy Leissinger, MD, called efanesoctocog alfa a “victory” for patients with hemophilia A.

“In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner – a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion,” wrote Dr. Leissinger, director of the Louisiana Center for Bleeding and Clotting Disorders at Tulane University in New Orleans.

Sanofi said that Altuviiio is expected to be commercially available in April 2023. The company said that it will price the product at parity to the annual cost of treating a prophylaxis patient with its Eloctate product (antihemophilic factor [recombinant], Fc fusion protein). Sanofi will provide comprehensive patient support services and resources online and at 1-855-MyALTUVIIIO (855-692-5888).

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

Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.

Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).

Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785

Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.

Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).

Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785

Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.

Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).

Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785

Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).

Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).

Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.

Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.

Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287

Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).

Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).

Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.

Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.

Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287

Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).

Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).

Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.

Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.

Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287

Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).

Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).

Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332

Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).

Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).

Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332

Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).

Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).

Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332

Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).

Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.

Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.

Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092

Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).

Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.

Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.

Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092

Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).

Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.

Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.

Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092

Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.

Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).

Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3

Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.

Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).

Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3

Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.

Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).

Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3