Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

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

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

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

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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