Breast Cancer ICYMI

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

Trastuzumab emtansine (T-DM1) is a suitable first-line therapy for patients with HER2-positive, advanced breast cancer who cannot receive taxane-based therapy, according to researchers.

Final results from the phase 3 MARIANNE trial revealed similar overall survival (OS) in patients who received T-DM1, T-DM1 plus pertuzumab, or trastuzumab plus a taxane (HT). All three regimens resulted in a median OS exceeding 50 months.

The incidence of grade 3 or higher adverse events (AEs) was highest in patients who received HT.

Edith A. Perez, MD, of Mayo Clinic Cancer Center in Jacksonville, Fla., and colleagues reported these results in Cancer.

The MARIANNE trial (NCT01120184) enrolled 1,095 adults with HER2-positive, advanced breast cancer. They were randomized to receive HT, T-DM1, or T-DM1 plus pertuzumab. Patients in the HT arm received trastuzumab plus paclitaxel or docetaxel according to the investigator’s discretion.

In all, 352 patients received HT (257 on docetaxel and 96 on paclitaxel), 361 patients received T-DM1 plus placebo, and 366 received T-DM1 plus pertuzumab.
 

Response and OS

In the primary analysis, the median OS was not reached in any treatment arm at a median follow-up of 35 months. The rate of objective response was 67.9% in the HT arm, 64.2% in the T-DM1 plus pertuzumab arm, and 59.7% in the T-DM1 arm. The median duration of response was 12.5 months, 21.2 months, and 20.7 months, respectively.

For the final OS analysis, the median duration of follow-up was 54 months. Roughly 70% of patients in each arm had received at least one treatment regimen during follow-up.

The final median OS was similar across the treatment arms – 50.9 months in the HT arm, 53.7 months in the T-DM1 arm, and 51.8 months in the T-DM1 plus pertuzumab arm. With the HT arm as a reference, the stratified hazard ratio was 0.93 for the T-DM1 arm and 0.86 for the T-DM1 plus pertuzumab arm.

OS results were consistent across subgroups. Although there were some differences in hazard ratios, “none of the examined subgroups showed a clear benefit with one treatment regimen in comparison with the others,” the researchers wrote.

The researchers also analyzed OS by response status at 6.5 months after randomization. Among nonresponders, the median OS was 41.9 months in the T-DM1 plus pertuzumab arm, 45.7 months in the T-DM1 arm, and 48.1 months in the HT arm. Among responders, the median OS was not reached in the T-DM1 plus pertuzumab arm, 64.4 months, and 56.3 months, respectively.

There were no baseline characteristics or biomarkers that were strongly associated with response by treatment group. However, in the HT and T-DM1 arms, patients with above-median HER2 messenger RNA expression were more likely to respond.
 

Safety

Rates of grade 3 or higher AEs were 55.8% in the HT arm, 47.1% in the T-DM1 arm, and 48.6% in the T-DM1 plus pertuzumab arm. The most common grade 3 or higher AEs were as follows:

• HT arm – neutropenia (19.3%), febrile neutropenia (6.5%), and diarrhea (4.2%).
• T-DM1 arm – increased aspartate aminotransferase (6.9%), thrombocytopenia (6.6%), and anemia (5.0%).
• T-DM1 plus pertuzumab arm – thrombocytopenia (9.0%), anemia (7.1%), and increased alanine aminotransferase (6.0%).

Rates of AE-related treatment discontinuation were 20.8% in the T-DM1 arm, 23.0% in the T-DM1 plus pertuzumab arm, and 30.6% in the HT arm. Rates of AE-related death were 1.4%, 1.9%, and 2.0%, respectively.

This study was funded by F. Hoffmann–La Roche. Dr. Perez was previously employed by Genentech/Roche. Her fellow authors disclosed relationships with Roche and many other companies.

SOURCE: Perez EA et al. Cancer. 2019 Jul 18. doi: 10.1002/cncr.32392.

Trastuzumab emtansine (T-DM1) is a suitable first-line therapy for patients with HER2-positive, advanced breast cancer who cannot receive taxane-based therapy, according to researchers.

Final results from the phase 3 MARIANNE trial revealed similar overall survival (OS) in patients who received T-DM1, T-DM1 plus pertuzumab, or trastuzumab plus a taxane (HT). All three regimens resulted in a median OS exceeding 50 months.

The incidence of grade 3 or higher adverse events (AEs) was highest in patients who received HT.

Edith A. Perez, MD, of Mayo Clinic Cancer Center in Jacksonville, Fla., and colleagues reported these results in Cancer.

The MARIANNE trial (NCT01120184) enrolled 1,095 adults with HER2-positive, advanced breast cancer. They were randomized to receive HT, T-DM1, or T-DM1 plus pertuzumab. Patients in the HT arm received trastuzumab plus paclitaxel or docetaxel according to the investigator’s discretion.

In all, 352 patients received HT (257 on docetaxel and 96 on paclitaxel), 361 patients received T-DM1 plus placebo, and 366 received T-DM1 plus pertuzumab.
 

Response and OS

In the primary analysis, the median OS was not reached in any treatment arm at a median follow-up of 35 months. The rate of objective response was 67.9% in the HT arm, 64.2% in the T-DM1 plus pertuzumab arm, and 59.7% in the T-DM1 arm. The median duration of response was 12.5 months, 21.2 months, and 20.7 months, respectively.

For the final OS analysis, the median duration of follow-up was 54 months. Roughly 70% of patients in each arm had received at least one treatment regimen during follow-up.

The final median OS was similar across the treatment arms – 50.9 months in the HT arm, 53.7 months in the T-DM1 arm, and 51.8 months in the T-DM1 plus pertuzumab arm. With the HT arm as a reference, the stratified hazard ratio was 0.93 for the T-DM1 arm and 0.86 for the T-DM1 plus pertuzumab arm.

OS results were consistent across subgroups. Although there were some differences in hazard ratios, “none of the examined subgroups showed a clear benefit with one treatment regimen in comparison with the others,” the researchers wrote.

The researchers also analyzed OS by response status at 6.5 months after randomization. Among nonresponders, the median OS was 41.9 months in the T-DM1 plus pertuzumab arm, 45.7 months in the T-DM1 arm, and 48.1 months in the HT arm. Among responders, the median OS was not reached in the T-DM1 plus pertuzumab arm, 64.4 months, and 56.3 months, respectively.

There were no baseline characteristics or biomarkers that were strongly associated with response by treatment group. However, in the HT and T-DM1 arms, patients with above-median HER2 messenger RNA expression were more likely to respond.
 

Safety

Rates of grade 3 or higher AEs were 55.8% in the HT arm, 47.1% in the T-DM1 arm, and 48.6% in the T-DM1 plus pertuzumab arm. The most common grade 3 or higher AEs were as follows:

• HT arm – neutropenia (19.3%), febrile neutropenia (6.5%), and diarrhea (4.2%).
• T-DM1 arm – increased aspartate aminotransferase (6.9%), thrombocytopenia (6.6%), and anemia (5.0%).
• T-DM1 plus pertuzumab arm – thrombocytopenia (9.0%), anemia (7.1%), and increased alanine aminotransferase (6.0%).

Rates of AE-related treatment discontinuation were 20.8% in the T-DM1 arm, 23.0% in the T-DM1 plus pertuzumab arm, and 30.6% in the HT arm. Rates of AE-related death were 1.4%, 1.9%, and 2.0%, respectively.

This study was funded by F. Hoffmann–La Roche. Dr. Perez was previously employed by Genentech/Roche. Her fellow authors disclosed relationships with Roche and many other companies.

SOURCE: Perez EA et al. Cancer. 2019 Jul 18. doi: 10.1002/cncr.32392.

Trastuzumab emtansine (T-DM1) is a suitable first-line therapy for patients with HER2-positive, advanced breast cancer who cannot receive taxane-based therapy, according to researchers.

Final results from the phase 3 MARIANNE trial revealed similar overall survival (OS) in patients who received T-DM1, T-DM1 plus pertuzumab, or trastuzumab plus a taxane (HT). All three regimens resulted in a median OS exceeding 50 months.

The incidence of grade 3 or higher adverse events (AEs) was highest in patients who received HT.

Edith A. Perez, MD, of Mayo Clinic Cancer Center in Jacksonville, Fla., and colleagues reported these results in Cancer.

The MARIANNE trial (NCT01120184) enrolled 1,095 adults with HER2-positive, advanced breast cancer. They were randomized to receive HT, T-DM1, or T-DM1 plus pertuzumab. Patients in the HT arm received trastuzumab plus paclitaxel or docetaxel according to the investigator’s discretion.

In all, 352 patients received HT (257 on docetaxel and 96 on paclitaxel), 361 patients received T-DM1 plus placebo, and 366 received T-DM1 plus pertuzumab.
 

Response and OS

In the primary analysis, the median OS was not reached in any treatment arm at a median follow-up of 35 months. The rate of objective response was 67.9% in the HT arm, 64.2% in the T-DM1 plus pertuzumab arm, and 59.7% in the T-DM1 arm. The median duration of response was 12.5 months, 21.2 months, and 20.7 months, respectively.

For the final OS analysis, the median duration of follow-up was 54 months. Roughly 70% of patients in each arm had received at least one treatment regimen during follow-up.

The final median OS was similar across the treatment arms – 50.9 months in the HT arm, 53.7 months in the T-DM1 arm, and 51.8 months in the T-DM1 plus pertuzumab arm. With the HT arm as a reference, the stratified hazard ratio was 0.93 for the T-DM1 arm and 0.86 for the T-DM1 plus pertuzumab arm.

OS results were consistent across subgroups. Although there were some differences in hazard ratios, “none of the examined subgroups showed a clear benefit with one treatment regimen in comparison with the others,” the researchers wrote.

The researchers also analyzed OS by response status at 6.5 months after randomization. Among nonresponders, the median OS was 41.9 months in the T-DM1 plus pertuzumab arm, 45.7 months in the T-DM1 arm, and 48.1 months in the HT arm. Among responders, the median OS was not reached in the T-DM1 plus pertuzumab arm, 64.4 months, and 56.3 months, respectively.

There were no baseline characteristics or biomarkers that were strongly associated with response by treatment group. However, in the HT and T-DM1 arms, patients with above-median HER2 messenger RNA expression were more likely to respond.
 

Safety

Rates of grade 3 or higher AEs were 55.8% in the HT arm, 47.1% in the T-DM1 arm, and 48.6% in the T-DM1 plus pertuzumab arm. The most common grade 3 or higher AEs were as follows:

• HT arm – neutropenia (19.3%), febrile neutropenia (6.5%), and diarrhea (4.2%).
• T-DM1 arm – increased aspartate aminotransferase (6.9%), thrombocytopenia (6.6%), and anemia (5.0%).
• T-DM1 plus pertuzumab arm – thrombocytopenia (9.0%), anemia (7.1%), and increased alanine aminotransferase (6.0%).

Rates of AE-related treatment discontinuation were 20.8% in the T-DM1 arm, 23.0% in the T-DM1 plus pertuzumab arm, and 30.6% in the HT arm. Rates of AE-related death were 1.4%, 1.9%, and 2.0%, respectively.

This study was funded by F. Hoffmann–La Roche. Dr. Perez was previously employed by Genentech/Roche. Her fellow authors disclosed relationships with Roche and many other companies.

SOURCE: Perez EA et al. Cancer. 2019 Jul 18. doi: 10.1002/cncr.32392.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

Standard adjuvant chemotherapy remained superior to capecitabine in older patients with early breast cancer, according to long-term follow-up results from a randomized study.

“We previously reported the primary analysis after a median follow-up of 2.4 years,” wrote Hyman B. Muss, MD, of the University of North Carolina, Chapel Hill, and his colleagues in Journal of Clinical Oncology.

“We now assess the risks and benefits of treatment after a median follow-up time of 11.4 years,” they said.

The Cancer and Leukemia Group B 49907 trial included 633 women aged 65 years and over with early breast cancer. Study patients were randomly assigned to receive either standard adjuvant chemotherapy (either cyclophosphamide and doxorubicin, methotrexate and fluorouracil, or cyclophosphamide) or capecitabine.

The study was designed to evaluate noninferiority of capecitabine versus standard chemotherapy. The primary outcome measured was recurrence-free survival (RFS); overall survival (OS) was included as a secondary endpoint.

After analysis, the researchers reported that the 10-year RFS rates were 56% with standard chemotherapy versus 50% with capecitabine (hazard ratio, 0.80; P = .03).

In addition, the breast cancer–specific survival rates were 88% and 82% in patients treated with standard chemotherapy, compared with capecitabine, respectively (hazard ratio, 0.62; P = .03). OS rates were 62% and 56% in the same groups (HR, 0.84; P = .16).

“With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease,” Dr. Muss and his colleagues wrote.

The researchers acknowledged that the presence of comorbidities in this older population may diminish overall survival benefits.

“Optimally, we must increase the number of older patients in cancer clinical trials to have accurate data on outcomes, especially toxicity, for newer agents,” they concluded.

The study was funded by the National Cancer Institute of the National Institutes of Health. The authors reported financial affiliations with Boehringer Ingelheim, Celgene, Genentech, Novartis, Puma Biotechnology, Pfizer, Sanofi, Seattle Genetics, and several others.

SOURCE: Muss HB et al. J Clin Oncol. 2019 Jul 24. doi: 10.1200/JCO.19.00647.

Standard adjuvant chemotherapy remained superior to capecitabine in older patients with early breast cancer, according to long-term follow-up results from a randomized study.

“We previously reported the primary analysis after a median follow-up of 2.4 years,” wrote Hyman B. Muss, MD, of the University of North Carolina, Chapel Hill, and his colleagues in Journal of Clinical Oncology.

“We now assess the risks and benefits of treatment after a median follow-up time of 11.4 years,” they said.

The Cancer and Leukemia Group B 49907 trial included 633 women aged 65 years and over with early breast cancer. Study patients were randomly assigned to receive either standard adjuvant chemotherapy (either cyclophosphamide and doxorubicin, methotrexate and fluorouracil, or cyclophosphamide) or capecitabine.

The study was designed to evaluate noninferiority of capecitabine versus standard chemotherapy. The primary outcome measured was recurrence-free survival (RFS); overall survival (OS) was included as a secondary endpoint.

After analysis, the researchers reported that the 10-year RFS rates were 56% with standard chemotherapy versus 50% with capecitabine (hazard ratio, 0.80; P = .03).

In addition, the breast cancer–specific survival rates were 88% and 82% in patients treated with standard chemotherapy, compared with capecitabine, respectively (hazard ratio, 0.62; P = .03). OS rates were 62% and 56% in the same groups (HR, 0.84; P = .16).

“With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease,” Dr. Muss and his colleagues wrote.

The researchers acknowledged that the presence of comorbidities in this older population may diminish overall survival benefits.

“Optimally, we must increase the number of older patients in cancer clinical trials to have accurate data on outcomes, especially toxicity, for newer agents,” they concluded.

The study was funded by the National Cancer Institute of the National Institutes of Health. The authors reported financial affiliations with Boehringer Ingelheim, Celgene, Genentech, Novartis, Puma Biotechnology, Pfizer, Sanofi, Seattle Genetics, and several others.

SOURCE: Muss HB et al. J Clin Oncol. 2019 Jul 24. doi: 10.1200/JCO.19.00647.

Standard adjuvant chemotherapy remained superior to capecitabine in older patients with early breast cancer, according to long-term follow-up results from a randomized study.

“We previously reported the primary analysis after a median follow-up of 2.4 years,” wrote Hyman B. Muss, MD, of the University of North Carolina, Chapel Hill, and his colleagues in Journal of Clinical Oncology.

“We now assess the risks and benefits of treatment after a median follow-up time of 11.4 years,” they said.

The Cancer and Leukemia Group B 49907 trial included 633 women aged 65 years and over with early breast cancer. Study patients were randomly assigned to receive either standard adjuvant chemotherapy (either cyclophosphamide and doxorubicin, methotrexate and fluorouracil, or cyclophosphamide) or capecitabine.

The study was designed to evaluate noninferiority of capecitabine versus standard chemotherapy. The primary outcome measured was recurrence-free survival (RFS); overall survival (OS) was included as a secondary endpoint.

After analysis, the researchers reported that the 10-year RFS rates were 56% with standard chemotherapy versus 50% with capecitabine (hazard ratio, 0.80; P = .03).

In addition, the breast cancer–specific survival rates were 88% and 82% in patients treated with standard chemotherapy, compared with capecitabine, respectively (hazard ratio, 0.62; P = .03). OS rates were 62% and 56% in the same groups (HR, 0.84; P = .16).

“With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease,” Dr. Muss and his colleagues wrote.

The researchers acknowledged that the presence of comorbidities in this older population may diminish overall survival benefits.

“Optimally, we must increase the number of older patients in cancer clinical trials to have accurate data on outcomes, especially toxicity, for newer agents,” they concluded.

The study was funded by the National Cancer Institute of the National Institutes of Health. The authors reported financial affiliations with Boehringer Ingelheim, Celgene, Genentech, Novartis, Puma Biotechnology, Pfizer, Sanofi, Seattle Genetics, and several others.

SOURCE: Muss HB et al. J Clin Oncol. 2019 Jul 24. doi: 10.1200/JCO.19.00647.

Obese children and adolescents with multiple sclerosis (MS) had twice as many relapses on first-line treatment as compared with their non-obese counterparts, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.

The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.

“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.

This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.

Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.

This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.

Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90^th percentile, according to the report.

Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.

A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.

Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).

Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.

“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.

Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.

SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997

Obese children and adolescents with multiple sclerosis (MS) had twice as many relapses on first-line treatment as compared with their non-obese counterparts, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.

The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.

“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.

This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.

Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.

This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.

Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90^th percentile, according to the report.

Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.

A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.

Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).

Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.

“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.

Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.

SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997

Obese children and adolescents with multiple sclerosis (MS) had twice as many relapses on first-line treatment as compared with their non-obese counterparts, results of a recent large, single-center study show. The rate of switching to second-line disease-modifying therapy was consequently about 50% higher among the obese children in the study, which included a total of 453 pediatric patients.

The link between obesity and treatment response suggests that the management of these younger patients with MS could be improved through weight loss or body mass index (BMI)-adjusted dosing, according to Peter Huppke, MD, of Georg August University in Göttingen, Germany, and co-investigators.

“The findings do not indicate that obesity promotes greater disease activity, but pharmacokinetic factors are more likely associated with treatment response,” Dr. Huppke and co-authors said in a report on their study, which was published online ahead of print July 15 in JAMA Neurology.

This is believed to be the first-ever study to find an association between BMI and treatment response in pediatric patients with MS, according to the authors, who said they also confirmed a link between obesity and MS.

Specifically, obesity increased MS susceptibility by two-fold as compared with healthy controls, a finding that they said adds to a small but growing body of evidence that high BMI is associated with increased risk of the disease in these younger individuals.

This retrospective study included 453 pediatric patients with MS treated at the Center for MS in Childhood and Adolescence in Göttingen, Germany between 1990 and 2016. About two-thirds were female and the mean age at MS diagnosis was about 14 years.

Of those patients, 126 (27.8%) were classified as obese based on a BMI greater than the 90^th percentile, according to the report.

Dr. Huppke and co-investigators found that high BMI was linked to a significantly increased odds of pediatric MS, with odds ratios of 2.19 (95% CI, 1.5-3.1; P < 0.001) in girls and 2.14 (95% CI, 1.3-3.5; P = 0.003) in boys.

A total of 277 of these pediatric patients received a first-line disease-modifying therapy for 6 months or longer, including 249 treated with interferon beta and 51 treated with glatiramer.

Relapses were more common in obese patients, according to the report. with an annualized relapse rate of 1.29, compared to just 0.72 for those who were not overweight (P < 0.001).

Consequently, likelihood of receiving a second-line treatment was about 1.5 times higher in the obese or extremely obese patients, investigators said.

“A healthy weight may potentially optimize treatment outcomes and reduce disease-related burden and health care costs,” they concluded in the report, adding that BMI-adjusted dosing may “increase the value” of first-line disease-modifying therapies.

Dr. Huppke reported disclosures related to Bayer Health Care, Merck Serono, and Novartis not associated with the current study.

SOURCE: Huppke B, et al. JAMA Neurol. 2019 Jul 15. doi: 10.1001/jamaneurol.2019.1997

Early nerve transfer surgery is safe and can provide significant functional improvement to patients with cervical spinal cord injury and tetraplegia, according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.

The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
 

Injury had occurred less than 18 months previously

Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.

Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.

Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
 

Grasp function improved significantly

Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.

Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.

The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
 

A novel technique

“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.

Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.

The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.

[email protected]

SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.

Early nerve transfer surgery is safe and can provide significant functional improvement to patients with cervical spinal cord injury and tetraplegia, according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.

The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
 

Injury had occurred less than 18 months previously

Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.

Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.

Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
 

Grasp function improved significantly

Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.

Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.

The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
 

A novel technique

“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.

Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.

The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.

[email protected]

SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.

Early nerve transfer surgery is safe and can provide significant functional improvement to patients with cervical spinal cord injury and tetraplegia, according to research published online July 4 ahead of print in the Lancet. Combining nerve transfer with tendon transfer may maximize the functional benefit of surgery.

The loss of upper extremity function after cervical spinal cord injury can reduce independence and social and vocational engagement. People with tetraplegia rank improvement in hand function as their most important goal. Tendon transfers have been the traditional method of restoring function, but interest in nerve transfers has been increasing with the publication of successful results. Nerve transfers can reanimate several muscles at once and require a smaller incision and shorter immobilization, compared with tendon transfers.
 

Injury had occurred less than 18 months previously

Natasha van Zyl, MBBS, a plastic and reconstructive surgeon at Austin Health in Melbourne, and colleagues conducted a prospective case series to examine the clinical and functional outcomes of nerve transfer surgery for the reanimation of upper limb function in patients with tetraplegia. The investigators also sought to compare these outcomes with published outcomes for tendon transfer surgery.

Between April 14, 2014, and Nov. 22, 2018, Dr. van Zyl and colleagues recruited consecutive patients of any age with early cervical spinal cord injury of motor level C5 and below. Injury was required to have occurred fewer than 18 months before enrollment. Eligible participants had been referred to a single center for upper extremity reanimation and were considered candidates for nerve transfer.

Every participant underwent single or multiple nerve transfers in one or both upper limbs, and some participants also underwent tendon transfers. The goal of surgery was the restoration of elbow extension, grasp, pinch, and hand opening. An independent assessor evaluated participants at baseline and at 12 months and 24 months after surgery. The primary outcome measures were the action research arm test (ARAT), the grasp release test (GRT), and the spinal cord independence measure (SCIM).
 

Grasp function improved significantly

Dr. van Zyl and colleagues recruited 16 participants with traumatic spinal cord injury who underwent 59 nerve transfers. Ten participants also underwent tendon transfers. The population’s mean age at time of injury was 27.3 years. Three patients were female. Motor vehicle accidents were the most common cause of injury (31%). Follow-up data at 24 months were unavailable for three patients.

Participants’ median ARAT total score significantly improved from 16.5 at baseline to 34.0 at 24 months. Median GRT total score significantly improved from 35.0 at baseline to 125.2 at 24 months. The population’s mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference. The mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months.

The researchers observed six adverse events related to the surgery, but none had sustained functional consequences. No patients had an increase in musculoskeletal or neuropathic pain. Four of the 50 nerve transfers with 24-month follow-up failed.
 

A novel technique

“This project is the first to comprehensively examine outcomes for early, multiple nerve transfer surgery in the upper limbs of people with tetraplegia following traumatic spinal cord injury and is the largest prospective series of nerve transfers reported in this population to date,” said Dr. van Zyl and colleagues. Study limitations included the small sample size, the high variability of spinal cord injury patterns, and the potential for the multiple procedures that each participant underwent to confound data analysis.

Future research could explore whether nerve transfers are beneficial at more than 24 months after spinal cord injury, wrote the authors. In addition, it is unclear whether function and strength continue to improve beyond 24 months after surgery.

The study was funded by the Institute for Safety, Compensation, and Recovery Research in Australia. The authors had no competing interests.

[email protected]

SOURCE: van Zyl N et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31143-2.

Among women with breast cancer, risk of death is more than twice as high for those who are childhood cancer survivors than for those in whom this cancer is their first, found a retrospective cohort study. However, the excess deaths are mainly from comorbidities related to previous therapies.

Breast cancer is among the leading subsequent malignancies in adult survivors of pediatric cancers, note the investigators, who were led by Chaya S. Moskowitz, PhD, of the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center in New York. But outcomes after this diagnosis are not well characterized.

The investigators used the Childhood Cancer Survivor Study to identify 274 female 5-year survivors of cancer diagnosed before age 21 years who received a subsequent breast cancer diagnosis at a median age of 38 years. They then used Surveillance, Epidemiology, and End Results data to identify a control group of 1,095 female patients with de novo breast cancer matched on age, race, stage, and year of breast cancer diagnosis.

The 10-year overall survival was 73% among the childhood cancer survivors, investigators reported in the Journal of Clinical Oncology.

Compared with the control women whose breast cancer was their first cancer, the women with breast cancer who were childhood cancer survivors had an elevated risk of death from any cause (hazard ratio, 2.2) that persisted after analyses were adjusted for receipt of chemotherapy and radiation therapy (HR, 2.4). In addition, findings were similar in analyses restricted to women with ductal carcinoma in situ and women with stage 1-3 breast cancer.

The childhood cancer survivors had a modestly elevated risk of dying from breast cancer (HR, 1.3) but a sharply elevated risk of dying from other health-related causes, including other subsequent malignancies and cardiovascular or pulmonary disease often related to previous therapies (HR, 5.5).

In addition, the childhood cancer survivors had a higher cumulative incidence of diagnosis of second asynchronous breast cancers a year or more later, relative to the women in whom breast cancer was their first cancer (P less than .001). The 5-year cumulative incidence was 8.0% among the childhood cancer survivors and just 2.7% among the control women.

“Although BC [breast cancer]-specific mortality was modestly higher in childhood cancer survivors, deaths attributable to health conditions other than BC seem to be the driving force in the elevated all-cause mortality,” Dr. Moskowitz and colleagues wrote.

“To change the dismal outcomes of these women, our results suggest that it is imperative that at the time of a secondary BC diagnosis, they have a comprehensive evaluation that extends beyond a singular focus of the BC,” they concluded. “This should include an assessment of existing cardiopulmonary disease and a plan for future cancer screening to optimize the management of comorbidities and cardiopulmonary disease and prolong the lifespan of these survivors.”

Dr. Moskowitz reported that she has a consulting or advisory role with Bioclinica. The study was supported by the National Cancer Institute, a Memorial Sloan Kettering Cancer Center Core grant, the Meg Berté Owen Foundation, and the American Lebanese Syrian Associated Charities.

SOURCE: Moskowitz CS et al. J Clin Oncol. 2019 Jul 1. doi: 10.1200/JCO.18.02219.

Among women with breast cancer, risk of death is more than twice as high for those who are childhood cancer survivors than for those in whom this cancer is their first, found a retrospective cohort study. However, the excess deaths are mainly from comorbidities related to previous therapies.

Breast cancer is among the leading subsequent malignancies in adult survivors of pediatric cancers, note the investigators, who were led by Chaya S. Moskowitz, PhD, of the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center in New York. But outcomes after this diagnosis are not well characterized.

The investigators used the Childhood Cancer Survivor Study to identify 274 female 5-year survivors of cancer diagnosed before age 21 years who received a subsequent breast cancer diagnosis at a median age of 38 years. They then used Surveillance, Epidemiology, and End Results data to identify a control group of 1,095 female patients with de novo breast cancer matched on age, race, stage, and year of breast cancer diagnosis.

The 10-year overall survival was 73% among the childhood cancer survivors, investigators reported in the Journal of Clinical Oncology.

Compared with the control women whose breast cancer was their first cancer, the women with breast cancer who were childhood cancer survivors had an elevated risk of death from any cause (hazard ratio, 2.2) that persisted after analyses were adjusted for receipt of chemotherapy and radiation therapy (HR, 2.4). In addition, findings were similar in analyses restricted to women with ductal carcinoma in situ and women with stage 1-3 breast cancer.

The childhood cancer survivors had a modestly elevated risk of dying from breast cancer (HR, 1.3) but a sharply elevated risk of dying from other health-related causes, including other subsequent malignancies and cardiovascular or pulmonary disease often related to previous therapies (HR, 5.5).

In addition, the childhood cancer survivors had a higher cumulative incidence of diagnosis of second asynchronous breast cancers a year or more later, relative to the women in whom breast cancer was their first cancer (P less than .001). The 5-year cumulative incidence was 8.0% among the childhood cancer survivors and just 2.7% among the control women.

“Although BC [breast cancer]-specific mortality was modestly higher in childhood cancer survivors, deaths attributable to health conditions other than BC seem to be the driving force in the elevated all-cause mortality,” Dr. Moskowitz and colleagues wrote.

“To change the dismal outcomes of these women, our results suggest that it is imperative that at the time of a secondary BC diagnosis, they have a comprehensive evaluation that extends beyond a singular focus of the BC,” they concluded. “This should include an assessment of existing cardiopulmonary disease and a plan for future cancer screening to optimize the management of comorbidities and cardiopulmonary disease and prolong the lifespan of these survivors.”

Dr. Moskowitz reported that she has a consulting or advisory role with Bioclinica. The study was supported by the National Cancer Institute, a Memorial Sloan Kettering Cancer Center Core grant, the Meg Berté Owen Foundation, and the American Lebanese Syrian Associated Charities.

SOURCE: Moskowitz CS et al. J Clin Oncol. 2019 Jul 1. doi: 10.1200/JCO.18.02219.

Among women with breast cancer, risk of death is more than twice as high for those who are childhood cancer survivors than for those in whom this cancer is their first, found a retrospective cohort study. However, the excess deaths are mainly from comorbidities related to previous therapies.

Breast cancer is among the leading subsequent malignancies in adult survivors of pediatric cancers, note the investigators, who were led by Chaya S. Moskowitz, PhD, of the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center in New York. But outcomes after this diagnosis are not well characterized.

The investigators used the Childhood Cancer Survivor Study to identify 274 female 5-year survivors of cancer diagnosed before age 21 years who received a subsequent breast cancer diagnosis at a median age of 38 years. They then used Surveillance, Epidemiology, and End Results data to identify a control group of 1,095 female patients with de novo breast cancer matched on age, race, stage, and year of breast cancer diagnosis.

The 10-year overall survival was 73% among the childhood cancer survivors, investigators reported in the Journal of Clinical Oncology.

Compared with the control women whose breast cancer was their first cancer, the women with breast cancer who were childhood cancer survivors had an elevated risk of death from any cause (hazard ratio, 2.2) that persisted after analyses were adjusted for receipt of chemotherapy and radiation therapy (HR, 2.4). In addition, findings were similar in analyses restricted to women with ductal carcinoma in situ and women with stage 1-3 breast cancer.

The childhood cancer survivors had a modestly elevated risk of dying from breast cancer (HR, 1.3) but a sharply elevated risk of dying from other health-related causes, including other subsequent malignancies and cardiovascular or pulmonary disease often related to previous therapies (HR, 5.5).

In addition, the childhood cancer survivors had a higher cumulative incidence of diagnosis of second asynchronous breast cancers a year or more later, relative to the women in whom breast cancer was their first cancer (P less than .001). The 5-year cumulative incidence was 8.0% among the childhood cancer survivors and just 2.7% among the control women.

“Although BC [breast cancer]-specific mortality was modestly higher in childhood cancer survivors, deaths attributable to health conditions other than BC seem to be the driving force in the elevated all-cause mortality,” Dr. Moskowitz and colleagues wrote.

“To change the dismal outcomes of these women, our results suggest that it is imperative that at the time of a secondary BC diagnosis, they have a comprehensive evaluation that extends beyond a singular focus of the BC,” they concluded. “This should include an assessment of existing cardiopulmonary disease and a plan for future cancer screening to optimize the management of comorbidities and cardiopulmonary disease and prolong the lifespan of these survivors.”

Dr. Moskowitz reported that she has a consulting or advisory role with Bioclinica. The study was supported by the National Cancer Institute, a Memorial Sloan Kettering Cancer Center Core grant, the Meg Berté Owen Foundation, and the American Lebanese Syrian Associated Charities.

SOURCE: Moskowitz CS et al. J Clin Oncol. 2019 Jul 1. doi: 10.1200/JCO.18.02219.

Mary Alissa Willis, MD, is the Medical Director for the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. We spoke with Dr. Willis about mental health issues in persons with MS and what health care facilities can do to better care for these patients.

What is the prevalence of depression in patients with MS?
Depression and anxiety are common in persons with multiple sclerosis (PwMS). In a systematic review, Ruth Ann Marrie, MD, PhD, and colleagues estimated the prevalence of depression in PwMS to be 23.7%. Approximately half of all PwMS experience depression at some point after their diagnosis.^1-3 This makes depression nearly twice as common in MS as in the general population.

What are some reasons patients with MS might begin to experience depression? What are some warning signs to look out for?

Many people assume that PwMS experience depression because of psychosocial stressors, unpredictability of disease progression, or poor coping strategies. Although these factors do contribute to depression, there is increasing evidence that immune dysregulation and structural changes in the brain caused by MS disease activity make some PwMS uniquely vulnerable to depression. Functional MRI studies have shown abnormalities in the prefrontal-subcortical network connectivity, which is involved in mood regulation. In addition, persistent somatic symptoms such as severe pain and fatigue limit daily activities and social participation—generally considered to be protective factors in depression.⁴ Warning signs for depression include loss of interest in activities, weight loss or weight gain, changes in sleep—too much or too little, an increase in fatigue, expressions of hopelessness or guilt, or increasing drug or alcohol use. 

What are some special considerations for patients with MS battling suicidal ideation?

Anthony Feinstein, MBBCh, MPhil, PhD, and colleagues reported that more than 28% of PwMS had suicidal ideation at some point.⁵ This is a huge number of people struggling with thoughts of suicide. Depression is a risk factor for suicide but other risks specific to PwMS include perceived loss of control, loss of job/income/social roles, loss of driving privileges, and marked physical or cognitive difficulties. While we are doing a better job screening for depression with quick screening tools such as the PHQ9, we could do better in suicide risk assessment.

What can health care providers do better to address depression and risk for suicide? What safety/preventative measures can they take?

 The first step in better addressing depression and risk for suicide is to directly ask patients. Pay attention to changes in appearance, behavior, requests for prescription refills, frequency of appointments, and who accompanies patients to appointments. Explore the reasons for these changes. It is important to respond proactively when comments or behavior suggest a patient at risk. Ask specific questions about plan, access to means, previous suicide attempts, and support network. Refer promptly for emergency or mental health services when appropriate. Familiarity with mental health colleagues, local crisis centers, and helplines can be helpful in engaging a team of people to provide assistance to a patient in need.

References

1. Marrie RA, Fisk JD, Tremlett H, et al. Differences in the burden of psychiatric comorbidity in MS vs the general population. Neurology. 2015;85(22):1972-1979.

2. Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol. 1990;47(1):98-104.

3. Marrie RA, Walld R, Bolton JM, et al; CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease. Estimating annual prevalence of depression and anxiety disorder in multiple sclerosis using administrative data. BMC Res Notes. 2017;10(1):619.

4. Passamonti L. Cerasa A, Liguori M, et al. Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis. Brain. 2009;132(pt 12):3380-3391.

5. Feinstein A. An examination of suicidal intent in patients with multiple sclerosis. Neurology. 2002;59(5):674-678.

Mary Alissa Willis, MD, is the Medical Director for the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. We spoke with Dr. Willis about mental health issues in persons with MS and what health care facilities can do to better care for these patients.

What is the prevalence of depression in patients with MS?
Depression and anxiety are common in persons with multiple sclerosis (PwMS). In a systematic review, Ruth Ann Marrie, MD, PhD, and colleagues estimated the prevalence of depression in PwMS to be 23.7%. Approximately half of all PwMS experience depression at some point after their diagnosis.^1-3 This makes depression nearly twice as common in MS as in the general population.

What are some reasons patients with MS might begin to experience depression? What are some warning signs to look out for?

Many people assume that PwMS experience depression because of psychosocial stressors, unpredictability of disease progression, or poor coping strategies. Although these factors do contribute to depression, there is increasing evidence that immune dysregulation and structural changes in the brain caused by MS disease activity make some PwMS uniquely vulnerable to depression. Functional MRI studies have shown abnormalities in the prefrontal-subcortical network connectivity, which is involved in mood regulation. In addition, persistent somatic symptoms such as severe pain and fatigue limit daily activities and social participation—generally considered to be protective factors in depression.⁴ Warning signs for depression include loss of interest in activities, weight loss or weight gain, changes in sleep—too much or too little, an increase in fatigue, expressions of hopelessness or guilt, or increasing drug or alcohol use. 

What are some special considerations for patients with MS battling suicidal ideation?

Anthony Feinstein, MBBCh, MPhil, PhD, and colleagues reported that more than 28% of PwMS had suicidal ideation at some point.⁵ This is a huge number of people struggling with thoughts of suicide. Depression is a risk factor for suicide but other risks specific to PwMS include perceived loss of control, loss of job/income/social roles, loss of driving privileges, and marked physical or cognitive difficulties. While we are doing a better job screening for depression with quick screening tools such as the PHQ9, we could do better in suicide risk assessment.

What can health care providers do better to address depression and risk for suicide? What safety/preventative measures can they take?

 The first step in better addressing depression and risk for suicide is to directly ask patients. Pay attention to changes in appearance, behavior, requests for prescription refills, frequency of appointments, and who accompanies patients to appointments. Explore the reasons for these changes. It is important to respond proactively when comments or behavior suggest a patient at risk. Ask specific questions about plan, access to means, previous suicide attempts, and support network. Refer promptly for emergency or mental health services when appropriate. Familiarity with mental health colleagues, local crisis centers, and helplines can be helpful in engaging a team of people to provide assistance to a patient in need.

References

1. Marrie RA, Fisk JD, Tremlett H, et al. Differences in the burden of psychiatric comorbidity in MS vs the general population. Neurology. 2015;85(22):1972-1979.

2. Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol. 1990;47(1):98-104.

3. Marrie RA, Walld R, Bolton JM, et al; CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease. Estimating annual prevalence of depression and anxiety disorder in multiple sclerosis using administrative data. BMC Res Notes. 2017;10(1):619.

4. Passamonti L. Cerasa A, Liguori M, et al. Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis. Brain. 2009;132(pt 12):3380-3391.

5. Feinstein A. An examination of suicidal intent in patients with multiple sclerosis. Neurology. 2002;59(5):674-678.

Mary Alissa Willis, MD, is the Medical Director for the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. We spoke with Dr. Willis about mental health issues in persons with MS and what health care facilities can do to better care for these patients.

What is the prevalence of depression in patients with MS?
Depression and anxiety are common in persons with multiple sclerosis (PwMS). In a systematic review, Ruth Ann Marrie, MD, PhD, and colleagues estimated the prevalence of depression in PwMS to be 23.7%. Approximately half of all PwMS experience depression at some point after their diagnosis.^1-3 This makes depression nearly twice as common in MS as in the general population.

What are some reasons patients with MS might begin to experience depression? What are some warning signs to look out for?

Many people assume that PwMS experience depression because of psychosocial stressors, unpredictability of disease progression, or poor coping strategies. Although these factors do contribute to depression, there is increasing evidence that immune dysregulation and structural changes in the brain caused by MS disease activity make some PwMS uniquely vulnerable to depression. Functional MRI studies have shown abnormalities in the prefrontal-subcortical network connectivity, which is involved in mood regulation. In addition, persistent somatic symptoms such as severe pain and fatigue limit daily activities and social participation—generally considered to be protective factors in depression.⁴ Warning signs for depression include loss of interest in activities, weight loss or weight gain, changes in sleep—too much or too little, an increase in fatigue, expressions of hopelessness or guilt, or increasing drug or alcohol use. 

What are some special considerations for patients with MS battling suicidal ideation?

Anthony Feinstein, MBBCh, MPhil, PhD, and colleagues reported that more than 28% of PwMS had suicidal ideation at some point.⁵ This is a huge number of people struggling with thoughts of suicide. Depression is a risk factor for suicide but other risks specific to PwMS include perceived loss of control, loss of job/income/social roles, loss of driving privileges, and marked physical or cognitive difficulties. While we are doing a better job screening for depression with quick screening tools such as the PHQ9, we could do better in suicide risk assessment.

What can health care providers do better to address depression and risk for suicide? What safety/preventative measures can they take?

 The first step in better addressing depression and risk for suicide is to directly ask patients. Pay attention to changes in appearance, behavior, requests for prescription refills, frequency of appointments, and who accompanies patients to appointments. Explore the reasons for these changes. It is important to respond proactively when comments or behavior suggest a patient at risk. Ask specific questions about plan, access to means, previous suicide attempts, and support network. Refer promptly for emergency or mental health services when appropriate. Familiarity with mental health colleagues, local crisis centers, and helplines can be helpful in engaging a team of people to provide assistance to a patient in need.

References

1. Marrie RA, Fisk JD, Tremlett H, et al. Differences in the burden of psychiatric comorbidity in MS vs the general population. Neurology. 2015;85(22):1972-1979.

2. Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol. 1990;47(1):98-104.

3. Marrie RA, Walld R, Bolton JM, et al; CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease. Estimating annual prevalence of depression and anxiety disorder in multiple sclerosis using administrative data. BMC Res Notes. 2017;10(1):619.

4. Passamonti L. Cerasa A, Liguori M, et al. Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis. Brain. 2009;132(pt 12):3380-3391.

5. Feinstein A. An examination of suicidal intent in patients with multiple sclerosis. Neurology. 2002;59(5):674-678.