Key clinical point: In patients with breast cancer (BC), premastectomy radiotherapy (PreMRT) followed by mastectomy and immediate breast reconstruction (IMBR) is feasible, safe, and shortens the time required for breast reconstruction.

Major finding: At a median follow-up of 29.7 months, there were no complete flap losses, locoregional recurrences, distant metastases, or deaths in the 48 patients who completed mastectomy with IMBR. Patients could undergo mastectomy with IMBR as early as 3 weeks (median 23 days) after completing radiotherapy. No grade 3-4 radiotherapy-related toxic effect or discontinuation of radiotherapy was reported.

Study details: The study enrolled 49 patients with T0-T3, N0-N3b, M0 BC from the phase 2 SAPHIRE trial who received PreMRT and were randomly assigned to receive hypofractionated or conventionally fractionated regional nodal irradiation, followed by mastectomy and IMBR.

Disclosures: This study was supported by the National Cancer Institute of the US National Institutes of Health and others. Five authors declared receiving grants from or having other ties with various sources.

Source: Schaverien MV, Singh P, Smith BD, et al. Premastectomy radiotherapy and immediate breast reconstruction: A randomized clinical trial. JAMA Netw Open. 2024;7(4):e245217 (Apr 5). doi: 10.1001/jamanetworkopen.2024.5217 Source

Key clinical point: In patients with breast cancer (BC), premastectomy radiotherapy (PreMRT) followed by mastectomy and immediate breast reconstruction (IMBR) is feasible, safe, and shortens the time required for breast reconstruction.

Major finding: At a median follow-up of 29.7 months, there were no complete flap losses, locoregional recurrences, distant metastases, or deaths in the 48 patients who completed mastectomy with IMBR. Patients could undergo mastectomy with IMBR as early as 3 weeks (median 23 days) after completing radiotherapy. No grade 3-4 radiotherapy-related toxic effect or discontinuation of radiotherapy was reported.

Study details: The study enrolled 49 patients with T0-T3, N0-N3b, M0 BC from the phase 2 SAPHIRE trial who received PreMRT and were randomly assigned to receive hypofractionated or conventionally fractionated regional nodal irradiation, followed by mastectomy and IMBR.

Disclosures: This study was supported by the National Cancer Institute of the US National Institutes of Health and others. Five authors declared receiving grants from or having other ties with various sources.

Source: Schaverien MV, Singh P, Smith BD, et al. Premastectomy radiotherapy and immediate breast reconstruction: A randomized clinical trial. JAMA Netw Open. 2024;7(4):e245217 (Apr 5). doi: 10.1001/jamanetworkopen.2024.5217 Source

Key clinical point: In patients with breast cancer (BC), premastectomy radiotherapy (PreMRT) followed by mastectomy and immediate breast reconstruction (IMBR) is feasible, safe, and shortens the time required for breast reconstruction.

Major finding: At a median follow-up of 29.7 months, there were no complete flap losses, locoregional recurrences, distant metastases, or deaths in the 48 patients who completed mastectomy with IMBR. Patients could undergo mastectomy with IMBR as early as 3 weeks (median 23 days) after completing radiotherapy. No grade 3-4 radiotherapy-related toxic effect or discontinuation of radiotherapy was reported.

Study details: The study enrolled 49 patients with T0-T3, N0-N3b, M0 BC from the phase 2 SAPHIRE trial who received PreMRT and were randomly assigned to receive hypofractionated or conventionally fractionated regional nodal irradiation, followed by mastectomy and IMBR.

Disclosures: This study was supported by the National Cancer Institute of the US National Institutes of Health and others. Five authors declared receiving grants from or having other ties with various sources.

Source: Schaverien MV, Singh P, Smith BD, et al. Premastectomy radiotherapy and immediate breast reconstruction: A randomized clinical trial. JAMA Netw Open. 2024;7(4):e245217 (Apr 5). doi: 10.1001/jamanetworkopen.2024.5217 Source

Key clinical point: Higher levels of tumor-infiltrating lymphocytes (TIL) in breast cancer tissue was associated with improved survival outcomes in patients with early-stage triple-negative breast cancer (TNBC) who received locoregional therapy but no adjuvant or neoadjuvant chemotherapy.

Major finding: At a median follow-up of 18 years, each 10% increase in TIL levels was associated with significantly improved invasive disease-free survival (adjusted hazard ratio [aHR] 0.92; 95% CI 0.89-0.94), overall survival (aHR 0.88; 95% CI 0.85-0.91), and recurrence-free survival outcomes (aHR 0.90; 95% CI 0.87-0.92).

Study details: This retrospective pooled analysis included 1966 patients with early-stage TNBC (stage I TNBC, 55%) who underwent surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy.

Disclosures: This study was partly supported by grants from the Breast Cancer Research Foundation and others. Several authors declared ties with various sources.

Source: Leon-Ferre RA, Jonas SF, Salgado R, et al, for the International Immuno-Oncology Biomarker Working Group. Tumor-infiltrating lymphocytes in triple-negative breast cancer. JAMA. 2024;331:1135-1144 (Apr 2). doi: 10.1001/jama.2024.3056 Source

Key clinical point: Higher levels of tumor-infiltrating lymphocytes (TIL) in breast cancer tissue was associated with improved survival outcomes in patients with early-stage triple-negative breast cancer (TNBC) who received locoregional therapy but no adjuvant or neoadjuvant chemotherapy.

Major finding: At a median follow-up of 18 years, each 10% increase in TIL levels was associated with significantly improved invasive disease-free survival (adjusted hazard ratio [aHR] 0.92; 95% CI 0.89-0.94), overall survival (aHR 0.88; 95% CI 0.85-0.91), and recurrence-free survival outcomes (aHR 0.90; 95% CI 0.87-0.92).

Study details: This retrospective pooled analysis included 1966 patients with early-stage TNBC (stage I TNBC, 55%) who underwent surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy.

Disclosures: This study was partly supported by grants from the Breast Cancer Research Foundation and others. Several authors declared ties with various sources.

Source: Leon-Ferre RA, Jonas SF, Salgado R, et al, for the International Immuno-Oncology Biomarker Working Group. Tumor-infiltrating lymphocytes in triple-negative breast cancer. JAMA. 2024;331:1135-1144 (Apr 2). doi: 10.1001/jama.2024.3056 Source

Key clinical point: Higher levels of tumor-infiltrating lymphocytes (TIL) in breast cancer tissue was associated with improved survival outcomes in patients with early-stage triple-negative breast cancer (TNBC) who received locoregional therapy but no adjuvant or neoadjuvant chemotherapy.

Major finding: At a median follow-up of 18 years, each 10% increase in TIL levels was associated with significantly improved invasive disease-free survival (adjusted hazard ratio [aHR] 0.92; 95% CI 0.89-0.94), overall survival (aHR 0.88; 95% CI 0.85-0.91), and recurrence-free survival outcomes (aHR 0.90; 95% CI 0.87-0.92).

Study details: This retrospective pooled analysis included 1966 patients with early-stage TNBC (stage I TNBC, 55%) who underwent surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy.

Disclosures: This study was partly supported by grants from the Breast Cancer Research Foundation and others. Several authors declared ties with various sources.

Source: Leon-Ferre RA, Jonas SF, Salgado R, et al, for the International Immuno-Oncology Biomarker Working Group. Tumor-infiltrating lymphocytes in triple-negative breast cancer. JAMA. 2024;331:1135-1144 (Apr 2). doi: 10.1001/jama.2024.3056 Source

Key clinical point: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone for 3 years significantly improved invasive disease-free survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (BC).

Major finding: At 3 years, ribociclib + NSAI vs NSAI alone led to a 25.2% lower risk for invasive disease, recurrence, or death (hazard ratio 0.75; two-sided P = .003), with an absolute invasive disease-free survival benefit of 3.3% (90.4% vs 87.1%). No new safety signals were reported.

Study details: This prespecified interim analysis of the phase 3 NATALEE trial included 5101 patients with HR+/HER2− stage II or III early BC who were randomly assigned to receive ribociclib (dosage 400 mg/day for 21 consecutive days followed by 7 days off; duration 36 months) in combination with an NSAI or NSAI alone.

Disclosures: The trial was funded by Novartis. Six authors declared being employees of or holding stocks in Novartis. Several authors declared ties with various sources, including Novartis.

Source: Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390:1080-1091 (Mar 20). doi: 10.1056/NEJMoa2305488 Source

Key clinical point: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone for 3 years significantly improved invasive disease-free survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (BC).

Major finding: At 3 years, ribociclib + NSAI vs NSAI alone led to a 25.2% lower risk for invasive disease, recurrence, or death (hazard ratio 0.75; two-sided P = .003), with an absolute invasive disease-free survival benefit of 3.3% (90.4% vs 87.1%). No new safety signals were reported.

Study details: This prespecified interim analysis of the phase 3 NATALEE trial included 5101 patients with HR+/HER2− stage II or III early BC who were randomly assigned to receive ribociclib (dosage 400 mg/day for 21 consecutive days followed by 7 days off; duration 36 months) in combination with an NSAI or NSAI alone.

Disclosures: The trial was funded by Novartis. Six authors declared being employees of or holding stocks in Novartis. Several authors declared ties with various sources, including Novartis.

Source: Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390:1080-1091 (Mar 20). doi: 10.1056/NEJMoa2305488 Source

Key clinical point: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone for 3 years significantly improved invasive disease-free survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (BC).

Major finding: At 3 years, ribociclib + NSAI vs NSAI alone led to a 25.2% lower risk for invasive disease, recurrence, or death (hazard ratio 0.75; two-sided P = .003), with an absolute invasive disease-free survival benefit of 3.3% (90.4% vs 87.1%). No new safety signals were reported.

Study details: This prespecified interim analysis of the phase 3 NATALEE trial included 5101 patients with HR+/HER2− stage II or III early BC who were randomly assigned to receive ribociclib (dosage 400 mg/day for 21 consecutive days followed by 7 days off; duration 36 months) in combination with an NSAI or NSAI alone.

Disclosures: The trial was funded by Novartis. Six authors declared being employees of or holding stocks in Novartis. Several authors declared ties with various sources, including Novartis.

Source: Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390:1080-1091 (Mar 20). doi: 10.1056/NEJMoa2305488 Source

Key clinical point: Recurrence-free survival after sentinel lymph node biopsy (SLNB) yielded noninferior outcomes compared to complete axillary lymph node dissection (ALND) in patients with clinically node-negative breast cancer (BC) and one or two sentinel-node macrometastases.

Major finding: The estimated 5-year recurrence-free survival was comparable in the SLNB alone vs completion ALND group (89.7% [95% CI 87.5%-91.9%] vs 88.7% [95% CI 86.3%-91.1%]), with the hazard ratio for recurrence or death being significantly below the noninferiority margin (0.89; P < .001 for non-inferiority).

Study details: Findings are from the noninferiority trial, SENOMAC, which included 2540 patients with clinically node-negative primary T1 to T3 BC with one or two sentinel lymph-node macrometastases who were randomly assigned to undergo SLNB alone (n = 1335) or completion ALND (n = 1205).

Disclosures: This study was supported by the Swedish Research Council and others. Oreste D. Gentilini declared serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: de Boniface J, Tvedskov TF, Rydén L, et al, for the SENOMAC Trialists’ Group. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024;390:1163-1175 (Apr 3). doi: 10.1056/NEJMoa2313487 Source

Key clinical point: Recurrence-free survival after sentinel lymph node biopsy (SLNB) yielded noninferior outcomes compared to complete axillary lymph node dissection (ALND) in patients with clinically node-negative breast cancer (BC) and one or two sentinel-node macrometastases.

Major finding: The estimated 5-year recurrence-free survival was comparable in the SLNB alone vs completion ALND group (89.7% [95% CI 87.5%-91.9%] vs 88.7% [95% CI 86.3%-91.1%]), with the hazard ratio for recurrence or death being significantly below the noninferiority margin (0.89; P < .001 for non-inferiority).

Study details: Findings are from the noninferiority trial, SENOMAC, which included 2540 patients with clinically node-negative primary T1 to T3 BC with one or two sentinel lymph-node macrometastases who were randomly assigned to undergo SLNB alone (n = 1335) or completion ALND (n = 1205).

Disclosures: This study was supported by the Swedish Research Council and others. Oreste D. Gentilini declared serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: de Boniface J, Tvedskov TF, Rydén L, et al, for the SENOMAC Trialists’ Group. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024;390:1163-1175 (Apr 3). doi: 10.1056/NEJMoa2313487 Source

Key clinical point: Recurrence-free survival after sentinel lymph node biopsy (SLNB) yielded noninferior outcomes compared to complete axillary lymph node dissection (ALND) in patients with clinically node-negative breast cancer (BC) and one or two sentinel-node macrometastases.

Major finding: The estimated 5-year recurrence-free survival was comparable in the SLNB alone vs completion ALND group (89.7% [95% CI 87.5%-91.9%] vs 88.7% [95% CI 86.3%-91.1%]), with the hazard ratio for recurrence or death being significantly below the noninferiority margin (0.89; P < .001 for non-inferiority).

Study details: Findings are from the noninferiority trial, SENOMAC, which included 2540 patients with clinically node-negative primary T1 to T3 BC with one or two sentinel lymph-node macrometastases who were randomly assigned to undergo SLNB alone (n = 1335) or completion ALND (n = 1205).

Disclosures: This study was supported by the Swedish Research Council and others. Oreste D. Gentilini declared serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: de Boniface J, Tvedskov TF, Rydén L, et al, for the SENOMAC Trialists’ Group. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024;390:1163-1175 (Apr 3). doi: 10.1056/NEJMoa2313487 Source

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

Co-administration of a probiotic and vitamin D significantly improved cognitive function in patients with schizophrenia, results from a double-blind randomized controlled trial suggested.

The combination also led to favorable changes in total cholesterol, fasting blood sugar, and a marker of inflammation.

“Targeting the microbiota-gut-brain axis with probiotic and vitamin D might provide a novel approach to promote mental health,” investigators led by Gita Sadighi, MD, Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran, wrote.

The study was published online in Neuropsychopharmacology Reports.
 

Cognitive Boost

The research includes data on 70 adults with schizophrenia who were on stable antipsychotic medication for at least 6 months. Half took a capsule containing five different probiotic strains plus 400 IU of vitamin D daily for 12 weeks, and half took a matching placebo capsule.

Primary outcomes were disease severity and cognitive function, measured at baseline, every 2 weeks during the trial, and again at the end of the study. Measurement tools included the Positive and Negative Syndrome Scale (PANSS) for disease severity and the 30-point Montreal Cognitive Assessment (MoCA) for cognitive function.

Secondary outcomes were lipid profile, body mass index, gastrointestinal problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate.

A total of 69 patients completed the trial, and no adverse effects were observed during the study period.

The marginal mean MoCA score increased by 1.96 units in the probiotic/vitamin D group compared with the placebo group during the study period, indicating significant improvement in cognitive function (P = .004).

In addition, the percentage of patients with a MoCA score of ≥ 26 (indicating normal cognition) increased significantly in the supplement group (P = .031), while there were no significant changes in the placebo group (P = .625).

The probiotic/vitamin D supplement was associated with a reduction in the PANSS score by 2.82 units compared with placebo, but the difference between groups was not statistically significant (P = .247).

The supplement group also saw a significant decrease in total cholesterol (P = .011), fasting blood sugar (P = .009), and CRP (P < .001).
 

Promising ‘Suggestive’ Evidence

Reached for comment, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Ontario, Canada, told this news organization that people living with schizophrenia have “significant impairment in general cognitive functions that can be debilitating and impair quality of life.”

This study provides “suggestive evidence” that the combination of probiotics and vitamin D is safe and effective in the treatment of cognitive dysfunction and “provides hope for persons with the lived experience. However, larger rigorous randomized control trials are needed to confirm these findings,” said Dr. McIntyre, who was not part of the study.

Also weighing in, Christopher M. Palmer, MD, assistant professor of psychiatry at Harvard Medical School in Boston, Massachusetts, noted that many researchers are focusing on the gut-brain connection and its role in a range of neuropsychiatric disorders, including schizophrenia.

“The gut microbiome appears to play a role in a range of factors that can impact brain function, including levels of inflammation, blood sugar, insulin signaling, and neurotransmitter production within the digestive tract,” said Dr. Palmer, who was not involved in the trial. “All of these factors can impact the brain, and in particular, brain metabolism, which increasingly is thought to play a key role in schizophrenia and other neuropsychiatric conditions.”

The new study builds on prior work in important ways, Dr. Palmer added. For example, he noted, earlier research did not show a benefit of probiotics alone.

“One of the challenges with probiotic research is the type of probiotic used. There are single-strain versions and multi-strain versions,” Dr. Palmer said. “This study used a probiotic containing five different bacterial species, so it’s possible that prior studies didn’t use the ideal type of probiotic. Combining the probiotic with vitamin D may also play a critical role.”

The new work replicates findings from a 2019 study in people with schizophrenia who received a four-strain probiotic plus vitamin D or a placebo for 12 weeks, he noted.

“The patients who got the probiotic plus vitamin D experienced improvement in psychiatric symptoms and improvement in three of the same biomarkers used in this study (reductions in total cholesterol, fasting blood sugar, and CRP),” Dr. Palmer said.

Like Dr. McIntyre, Dr. Palmer noted that larger clinical trials are needed before a treatment recommendation can be made.

“We also need to better understand which probiotics to use and the optimal dose of vitamin D supplementation,” he said. “In the meantime, however, patients may want to discuss this research with their clinicians to see if this might be something to consider in their own treatment.”

The study had no funding source. The authors and Dr. McIntyre had no relevant disclosures. Dr. Palmer is the author of the book Brain Energy published by Penguin Random House.

A version of this article appeared on Medscape.com.

Co-administration of a probiotic and vitamin D significantly improved cognitive function in patients with schizophrenia, results from a double-blind randomized controlled trial suggested.

The combination also led to favorable changes in total cholesterol, fasting blood sugar, and a marker of inflammation.

“Targeting the microbiota-gut-brain axis with probiotic and vitamin D might provide a novel approach to promote mental health,” investigators led by Gita Sadighi, MD, Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran, wrote.

The study was published online in Neuropsychopharmacology Reports.
 

Cognitive Boost

The research includes data on 70 adults with schizophrenia who were on stable antipsychotic medication for at least 6 months. Half took a capsule containing five different probiotic strains plus 400 IU of vitamin D daily for 12 weeks, and half took a matching placebo capsule.

Primary outcomes were disease severity and cognitive function, measured at baseline, every 2 weeks during the trial, and again at the end of the study. Measurement tools included the Positive and Negative Syndrome Scale (PANSS) for disease severity and the 30-point Montreal Cognitive Assessment (MoCA) for cognitive function.

Secondary outcomes were lipid profile, body mass index, gastrointestinal problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate.

A total of 69 patients completed the trial, and no adverse effects were observed during the study period.

The marginal mean MoCA score increased by 1.96 units in the probiotic/vitamin D group compared with the placebo group during the study period, indicating significant improvement in cognitive function (P = .004).

In addition, the percentage of patients with a MoCA score of ≥ 26 (indicating normal cognition) increased significantly in the supplement group (P = .031), while there were no significant changes in the placebo group (P = .625).

The probiotic/vitamin D supplement was associated with a reduction in the PANSS score by 2.82 units compared with placebo, but the difference between groups was not statistically significant (P = .247).

The supplement group also saw a significant decrease in total cholesterol (P = .011), fasting blood sugar (P = .009), and CRP (P < .001).
 

Promising ‘Suggestive’ Evidence

Reached for comment, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Ontario, Canada, told this news organization that people living with schizophrenia have “significant impairment in general cognitive functions that can be debilitating and impair quality of life.”

This study provides “suggestive evidence” that the combination of probiotics and vitamin D is safe and effective in the treatment of cognitive dysfunction and “provides hope for persons with the lived experience. However, larger rigorous randomized control trials are needed to confirm these findings,” said Dr. McIntyre, who was not part of the study.

Also weighing in, Christopher M. Palmer, MD, assistant professor of psychiatry at Harvard Medical School in Boston, Massachusetts, noted that many researchers are focusing on the gut-brain connection and its role in a range of neuropsychiatric disorders, including schizophrenia.

“The gut microbiome appears to play a role in a range of factors that can impact brain function, including levels of inflammation, blood sugar, insulin signaling, and neurotransmitter production within the digestive tract,” said Dr. Palmer, who was not involved in the trial. “All of these factors can impact the brain, and in particular, brain metabolism, which increasingly is thought to play a key role in schizophrenia and other neuropsychiatric conditions.”

The new study builds on prior work in important ways, Dr. Palmer added. For example, he noted, earlier research did not show a benefit of probiotics alone.

“One of the challenges with probiotic research is the type of probiotic used. There are single-strain versions and multi-strain versions,” Dr. Palmer said. “This study used a probiotic containing five different bacterial species, so it’s possible that prior studies didn’t use the ideal type of probiotic. Combining the probiotic with vitamin D may also play a critical role.”

The new work replicates findings from a 2019 study in people with schizophrenia who received a four-strain probiotic plus vitamin D or a placebo for 12 weeks, he noted.

“The patients who got the probiotic plus vitamin D experienced improvement in psychiatric symptoms and improvement in three of the same biomarkers used in this study (reductions in total cholesterol, fasting blood sugar, and CRP),” Dr. Palmer said.

Like Dr. McIntyre, Dr. Palmer noted that larger clinical trials are needed before a treatment recommendation can be made.

“We also need to better understand which probiotics to use and the optimal dose of vitamin D supplementation,” he said. “In the meantime, however, patients may want to discuss this research with their clinicians to see if this might be something to consider in their own treatment.”

The study had no funding source. The authors and Dr. McIntyre had no relevant disclosures. Dr. Palmer is the author of the book Brain Energy published by Penguin Random House.

A version of this article appeared on Medscape.com.

Co-administration of a probiotic and vitamin D significantly improved cognitive function in patients with schizophrenia, results from a double-blind randomized controlled trial suggested.

The combination also led to favorable changes in total cholesterol, fasting blood sugar, and a marker of inflammation.

“Targeting the microbiota-gut-brain axis with probiotic and vitamin D might provide a novel approach to promote mental health,” investigators led by Gita Sadighi, MD, Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran, wrote.

The study was published online in Neuropsychopharmacology Reports.
 

Cognitive Boost

The research includes data on 70 adults with schizophrenia who were on stable antipsychotic medication for at least 6 months. Half took a capsule containing five different probiotic strains plus 400 IU of vitamin D daily for 12 weeks, and half took a matching placebo capsule.

Primary outcomes were disease severity and cognitive function, measured at baseline, every 2 weeks during the trial, and again at the end of the study. Measurement tools included the Positive and Negative Syndrome Scale (PANSS) for disease severity and the 30-point Montreal Cognitive Assessment (MoCA) for cognitive function.

Secondary outcomes were lipid profile, body mass index, gastrointestinal problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate.

A total of 69 patients completed the trial, and no adverse effects were observed during the study period.

The marginal mean MoCA score increased by 1.96 units in the probiotic/vitamin D group compared with the placebo group during the study period, indicating significant improvement in cognitive function (P = .004).

In addition, the percentage of patients with a MoCA score of ≥ 26 (indicating normal cognition) increased significantly in the supplement group (P = .031), while there were no significant changes in the placebo group (P = .625).

The probiotic/vitamin D supplement was associated with a reduction in the PANSS score by 2.82 units compared with placebo, but the difference between groups was not statistically significant (P = .247).

The supplement group also saw a significant decrease in total cholesterol (P = .011), fasting blood sugar (P = .009), and CRP (P < .001).
 

Promising ‘Suggestive’ Evidence

Reached for comment, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Ontario, Canada, told this news organization that people living with schizophrenia have “significant impairment in general cognitive functions that can be debilitating and impair quality of life.”

This study provides “suggestive evidence” that the combination of probiotics and vitamin D is safe and effective in the treatment of cognitive dysfunction and “provides hope for persons with the lived experience. However, larger rigorous randomized control trials are needed to confirm these findings,” said Dr. McIntyre, who was not part of the study.

Also weighing in, Christopher M. Palmer, MD, assistant professor of psychiatry at Harvard Medical School in Boston, Massachusetts, noted that many researchers are focusing on the gut-brain connection and its role in a range of neuropsychiatric disorders, including schizophrenia.

“The gut microbiome appears to play a role in a range of factors that can impact brain function, including levels of inflammation, blood sugar, insulin signaling, and neurotransmitter production within the digestive tract,” said Dr. Palmer, who was not involved in the trial. “All of these factors can impact the brain, and in particular, brain metabolism, which increasingly is thought to play a key role in schizophrenia and other neuropsychiatric conditions.”

The new study builds on prior work in important ways, Dr. Palmer added. For example, he noted, earlier research did not show a benefit of probiotics alone.

“One of the challenges with probiotic research is the type of probiotic used. There are single-strain versions and multi-strain versions,” Dr. Palmer said. “This study used a probiotic containing five different bacterial species, so it’s possible that prior studies didn’t use the ideal type of probiotic. Combining the probiotic with vitamin D may also play a critical role.”

The new work replicates findings from a 2019 study in people with schizophrenia who received a four-strain probiotic plus vitamin D or a placebo for 12 weeks, he noted.

“The patients who got the probiotic plus vitamin D experienced improvement in psychiatric symptoms and improvement in three of the same biomarkers used in this study (reductions in total cholesterol, fasting blood sugar, and CRP),” Dr. Palmer said.

Like Dr. McIntyre, Dr. Palmer noted that larger clinical trials are needed before a treatment recommendation can be made.

“We also need to better understand which probiotics to use and the optimal dose of vitamin D supplementation,” he said. “In the meantime, however, patients may want to discuss this research with their clinicians to see if this might be something to consider in their own treatment.”

The study had no funding source. The authors and Dr. McIntyre had no relevant disclosures. Dr. Palmer is the author of the book Brain Energy published by Penguin Random House.

A version of this article appeared on Medscape.com.

Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.

Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.

“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.

“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.

The study was published online in JAMA Network Open.

MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.

To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.

The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).

Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
 

‘Sobering’ Findings

After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).

These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.

MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).

Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).

Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.

In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.

“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”

They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”

The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
 

A version of this article appeared on Medscape.com.

Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.

Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.

“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.

“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.

The study was published online in JAMA Network Open.

MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.

To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.

The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).

Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
 

‘Sobering’ Findings

After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).

These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.

MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).

Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).

Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.

In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.

“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”

They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”

The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
 

A version of this article appeared on Medscape.com.

Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.

Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.

“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.

“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.

The study was published online in JAMA Network Open.

MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.

To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.

The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).

Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
 

‘Sobering’ Findings

After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).

These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.

MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).

Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).

Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.

In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.

“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”

They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”

The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
 

A version of this article appeared on Medscape.com.

TOPLINE:

High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.

METHODOLOGY:

• The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
• The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
• The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.

TAKEAWAY:

• Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
• Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
• The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
• In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
• The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.

IN PRACTICE:

“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.

SOURCE:

Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.

LIMITATIONS:

The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.

DISCLOSURES:

This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.

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

TOPLINE:

High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.

METHODOLOGY:

• The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
• The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
• The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.

TAKEAWAY:

• Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
• Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
• The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
• In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
• The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.

IN PRACTICE:

“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.

SOURCE:

Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.

LIMITATIONS:

The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.

DISCLOSURES:

This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.

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

TOPLINE:

High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.

METHODOLOGY:

• The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
• The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
• The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.

TAKEAWAY:

• Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
• Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
• The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
• In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
• The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.

IN PRACTICE:

“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.

SOURCE:

Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.

LIMITATIONS:

The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.

DISCLOSURES:

This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.

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

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

BALTIMORE — Patients who have complications after dermatologic cosmetic procedures are prone to high rates of a host of mental health issues, ranging from anxiety disorder and depression to body dysmorphic disorder (BDD) and posttraumatic stress disorder (PTSD), according to a survey-based study of patients with dermatology-related complications. 

The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.

Taryn Murray, MD

“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
 

Rise in Mental Health Issues

The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results. 

Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.

“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”

Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”

The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).

The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).

Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.

“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
 

Take-Home Lesson

The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”

She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”

She said she hopes her findings lead to more research in the future.

Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”

She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.

The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”

Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.

A version of this article appeared on Medscape.com.

BALTIMORE — Patients who have complications after dermatologic cosmetic procedures are prone to high rates of a host of mental health issues, ranging from anxiety disorder and depression to body dysmorphic disorder (BDD) and posttraumatic stress disorder (PTSD), according to a survey-based study of patients with dermatology-related complications. 

The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.

Taryn Murray, MD

“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
 

Rise in Mental Health Issues

The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results. 

Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.

“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”

Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”

The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).

The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).

Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.

“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
 

Take-Home Lesson

The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”

She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”

She said she hopes her findings lead to more research in the future.

Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”

She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.

The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”

Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.

A version of this article appeared on Medscape.com.

BALTIMORE — Patients who have complications after dermatologic cosmetic procedures are prone to high rates of a host of mental health issues, ranging from anxiety disorder and depression to body dysmorphic disorder (BDD) and posttraumatic stress disorder (PTSD), according to a survey-based study of patients with dermatology-related complications. 

The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.

Taryn Murray, MD

“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
 

Rise in Mental Health Issues

The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results. 

Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.

“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”

Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”

The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).

The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).

Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.

“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
 

Take-Home Lesson

The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”

She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”

She said she hopes her findings lead to more research in the future.

Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”

She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.

The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”

Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.

A version of this article appeared on Medscape.com.