Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.