Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

The FP noted that the lesion had a central keratin core (resembling a volcano) surrounded by a somewhat pearly raised border. He suspected that this was a squamous cell carcinoma (SCC) of the keratoacanthoma type and recommended a biopsy.

A shave biopsy was performed, and the result confirmed the diagnosis of SCC of the keratoacanthoma type. (See the Watch & Learn video on “Shave biopsy.”) The pathologist added that the lesion was well-differentiated (which was to be expected with a keratoacanthoma). While some keratoacanthomas actually resolve spontaneously, the standard of care is to treat them with either excision, electrodesiccation and curettage, or cryotherapy. On the follow-up visit, these options were presented to the patient and he decided to have cryotherapy. He accepted the risk of hypopigmentation in the treated area, but said that he preferred to avoid surgery.

The area was anesthetized with an injection of 1% lidocaine and epinephrine, and cryotherapy was performed with a 5 mm margin. The area was frozen with liquid nitrogen spray for 30 seconds and allowed to thaw. A second freeze for 30 seconds was then applied. Sun protection and sun avoidance were encouraged. At a 1-year follow-up, there was no recurrence and there was hypopigmentation at the treatment site.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Guzman A, Usatine R. Keratoacanthoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:977-980.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP noted that the lesion had a central keratin core (resembling a volcano) surrounded by a somewhat pearly raised border. He suspected that this was a squamous cell carcinoma (SCC) of the keratoacanthoma type and recommended a biopsy.

A shave biopsy was performed, and the result confirmed the diagnosis of SCC of the keratoacanthoma type. (See the Watch & Learn video on “Shave biopsy.”) The pathologist added that the lesion was well-differentiated (which was to be expected with a keratoacanthoma). While some keratoacanthomas actually resolve spontaneously, the standard of care is to treat them with either excision, electrodesiccation and curettage, or cryotherapy. On the follow-up visit, these options were presented to the patient and he decided to have cryotherapy. He accepted the risk of hypopigmentation in the treated area, but said that he preferred to avoid surgery.

The area was anesthetized with an injection of 1% lidocaine and epinephrine, and cryotherapy was performed with a 5 mm margin. The area was frozen with liquid nitrogen spray for 30 seconds and allowed to thaw. A second freeze for 30 seconds was then applied. Sun protection and sun avoidance were encouraged. At a 1-year follow-up, there was no recurrence and there was hypopigmentation at the treatment site.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Guzman A, Usatine R. Keratoacanthoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:977-980.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP noted that the lesion had a central keratin core (resembling a volcano) surrounded by a somewhat pearly raised border. He suspected that this was a squamous cell carcinoma (SCC) of the keratoacanthoma type and recommended a biopsy.

A shave biopsy was performed, and the result confirmed the diagnosis of SCC of the keratoacanthoma type. (See the Watch & Learn video on “Shave biopsy.”) The pathologist added that the lesion was well-differentiated (which was to be expected with a keratoacanthoma). While some keratoacanthomas actually resolve spontaneously, the standard of care is to treat them with either excision, electrodesiccation and curettage, or cryotherapy. On the follow-up visit, these options were presented to the patient and he decided to have cryotherapy. He accepted the risk of hypopigmentation in the treated area, but said that he preferred to avoid surgery.

The area was anesthetized with an injection of 1% lidocaine and epinephrine, and cryotherapy was performed with a 5 mm margin. The area was frozen with liquid nitrogen spray for 30 seconds and allowed to thaw. A second freeze for 30 seconds was then applied. Sun protection and sun avoidance were encouraged. At a 1-year follow-up, there was no recurrence and there was hypopigmentation at the treatment site.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Guzman A, Usatine R. Keratoacanthoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:977-980.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Two reports in the BMJ regarding new research offer grim tidings about mortality in the United States: One study has suggested the opioid epidemic is driving down life expectancy, and another has found that midlife death rates from multiple causes are on the rise across ethnic groups.

“Death rates are increasing across the U.S. population for dozens of conditions,” according to Steven H. Woolf, MD, MPH, a professor at Virginia Commonwealth University, Richmond, and his associates, who together wrote the second study. “Of particular urgency is recognizing that the unfavorable mortality pattern that began for some groups in the 1990s is now unfolding among Hispanics and non-Hispanic blacks, a development made more consequential by their high baseline mortality rates.”

Dr. Woolf and his coinvestigators tracked midlife mortality (ages 25-64 years) from 1999-2016 across the U.S. population.

They found that all-cause mortality jumped among whites, American Indians, and Alaska Natives over that time. A trend toward decreasing all-cause mortality ended in 2009-2011 among African Americans, Hispanic American, Asian Americans, and Americans of Pacific Islander descent.

“Drug overdoses were the leading cause of increased mortality in midlife in each population, but mortality also increased for alcohol related conditions, suicides, and organ diseases involving multiple body systems,” according to the researchers.

For the life expectancy study, which was published in the BMJ, researchers led by Jessica Y. Ho, PhD, of the University of Southern California, Los Angeles, tracked all-cause and cause-specific mortality in 18 high-income nations. They focused on the years 2014-2016.

Most of the nations saw declines in life expectancy from 2014-2015, mainly caused by older people dying from physical diseases and mental disorders. From 2015-2016, most of these nations saw their life expectancy levels rebound and experienced “robust gains.”

In the United States, however, life expectancy at birth for women fell from 81.47 years in 2014 to 81.35 years in 2015, and rose to 81.40 years in 2016.

For men, life expectancy fell continuously from 76.67 years in 2014 to 76.50 years in 2015 to 76.40 years in 2016.

In 2016, these life expectancies were the lowest of 17 nations examined in the study. (Statistics from the 18th nation in the study, Canada, were not included for 2016).

The United States was an outlier in other ways. For one, deaths among people younger than 65 years were the major contributor to the life expectancy decline.

And causes of death were also different than other countries: “For American women, drug overdose and external causes, and respiratory and cardiovascular diseases, contributed roughly equally to the decline in life expectancy, but for American men, nearly all of the decline was attributable to drug overdose and external causes.”

No funding is reported for the death rates study. The study authors report no relevant disclosures.

The life expectancy study was supported by the Robert Wood Johnson Foundation. Authors variously report support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, and the National Institute of Child Health and Human Development.

SOURCE: Ho JY et al. BMJ. 2018;362:k2562; Woolf SH et al. BMJ 2018;362:k3096.

Two reports in the BMJ regarding new research offer grim tidings about mortality in the United States: One study has suggested the opioid epidemic is driving down life expectancy, and another has found that midlife death rates from multiple causes are on the rise across ethnic groups.

“Death rates are increasing across the U.S. population for dozens of conditions,” according to Steven H. Woolf, MD, MPH, a professor at Virginia Commonwealth University, Richmond, and his associates, who together wrote the second study. “Of particular urgency is recognizing that the unfavorable mortality pattern that began for some groups in the 1990s is now unfolding among Hispanics and non-Hispanic blacks, a development made more consequential by their high baseline mortality rates.”

Dr. Woolf and his coinvestigators tracked midlife mortality (ages 25-64 years) from 1999-2016 across the U.S. population.

They found that all-cause mortality jumped among whites, American Indians, and Alaska Natives over that time. A trend toward decreasing all-cause mortality ended in 2009-2011 among African Americans, Hispanic American, Asian Americans, and Americans of Pacific Islander descent.

“Drug overdoses were the leading cause of increased mortality in midlife in each population, but mortality also increased for alcohol related conditions, suicides, and organ diseases involving multiple body systems,” according to the researchers.

For the life expectancy study, which was published in the BMJ, researchers led by Jessica Y. Ho, PhD, of the University of Southern California, Los Angeles, tracked all-cause and cause-specific mortality in 18 high-income nations. They focused on the years 2014-2016.

Most of the nations saw declines in life expectancy from 2014-2015, mainly caused by older people dying from physical diseases and mental disorders. From 2015-2016, most of these nations saw their life expectancy levels rebound and experienced “robust gains.”

In the United States, however, life expectancy at birth for women fell from 81.47 years in 2014 to 81.35 years in 2015, and rose to 81.40 years in 2016.

For men, life expectancy fell continuously from 76.67 years in 2014 to 76.50 years in 2015 to 76.40 years in 2016.

In 2016, these life expectancies were the lowest of 17 nations examined in the study. (Statistics from the 18th nation in the study, Canada, were not included for 2016).

The United States was an outlier in other ways. For one, deaths among people younger than 65 years were the major contributor to the life expectancy decline.

And causes of death were also different than other countries: “For American women, drug overdose and external causes, and respiratory and cardiovascular diseases, contributed roughly equally to the decline in life expectancy, but for American men, nearly all of the decline was attributable to drug overdose and external causes.”

No funding is reported for the death rates study. The study authors report no relevant disclosures.

The life expectancy study was supported by the Robert Wood Johnson Foundation. Authors variously report support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, and the National Institute of Child Health and Human Development.

SOURCE: Ho JY et al. BMJ. 2018;362:k2562; Woolf SH et al. BMJ 2018;362:k3096.

Two reports in the BMJ regarding new research offer grim tidings about mortality in the United States: One study has suggested the opioid epidemic is driving down life expectancy, and another has found that midlife death rates from multiple causes are on the rise across ethnic groups.

“Death rates are increasing across the U.S. population for dozens of conditions,” according to Steven H. Woolf, MD, MPH, a professor at Virginia Commonwealth University, Richmond, and his associates, who together wrote the second study. “Of particular urgency is recognizing that the unfavorable mortality pattern that began for some groups in the 1990s is now unfolding among Hispanics and non-Hispanic blacks, a development made more consequential by their high baseline mortality rates.”

Dr. Woolf and his coinvestigators tracked midlife mortality (ages 25-64 years) from 1999-2016 across the U.S. population.

They found that all-cause mortality jumped among whites, American Indians, and Alaska Natives over that time. A trend toward decreasing all-cause mortality ended in 2009-2011 among African Americans, Hispanic American, Asian Americans, and Americans of Pacific Islander descent.

“Drug overdoses were the leading cause of increased mortality in midlife in each population, but mortality also increased for alcohol related conditions, suicides, and organ diseases involving multiple body systems,” according to the researchers.

For the life expectancy study, which was published in the BMJ, researchers led by Jessica Y. Ho, PhD, of the University of Southern California, Los Angeles, tracked all-cause and cause-specific mortality in 18 high-income nations. They focused on the years 2014-2016.

Most of the nations saw declines in life expectancy from 2014-2015, mainly caused by older people dying from physical diseases and mental disorders. From 2015-2016, most of these nations saw their life expectancy levels rebound and experienced “robust gains.”

In the United States, however, life expectancy at birth for women fell from 81.47 years in 2014 to 81.35 years in 2015, and rose to 81.40 years in 2016.

For men, life expectancy fell continuously from 76.67 years in 2014 to 76.50 years in 2015 to 76.40 years in 2016.

In 2016, these life expectancies were the lowest of 17 nations examined in the study. (Statistics from the 18th nation in the study, Canada, were not included for 2016).

The United States was an outlier in other ways. For one, deaths among people younger than 65 years were the major contributor to the life expectancy decline.

And causes of death were also different than other countries: “For American women, drug overdose and external causes, and respiratory and cardiovascular diseases, contributed roughly equally to the decline in life expectancy, but for American men, nearly all of the decline was attributable to drug overdose and external causes.”

No funding is reported for the death rates study. The study authors report no relevant disclosures.

The life expectancy study was supported by the Robert Wood Johnson Foundation. Authors variously report support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, and the National Institute of Child Health and Human Development.

SOURCE: Ho JY et al. BMJ. 2018;362:k2562; Woolf SH et al. BMJ 2018;362:k3096.

In combination with an optimized background regimen, the humanized IgG4 monoclonal antibody ibalizumab can reduce viral load and increase CD4 counts in patients with multidrug-resistant HIV type 1 (MDR HIV-1), according to a study published in the New England Journal of Medicine. It does so by binding noncompetitively to CD4 receptors, which can thereby block HIV-1 entry.

copyright alexskopje/Thinkstock

TMB-301 (NCT02475629) was a 24-week, open-label, single-group, phase 3 study that included patients with MDR HIV-1. During July 2015 to October 2016, patients first continued on their previous treatment for 7 days, then were given a 2,000-mg loading dose of ibalizumab as monotherapy, and then continued on 800 mg ibalizumab every 14 days plus an individualized regimen that was optimized based on patients’ past treatments for the remainder of the study period.

The primary endpoint was how many patients experienced a decrease in viral load of at least 0.5 log₁₀ copies/mL from baseline to day 14 – that is, after the 7-day control period plus the 7-days ibalizumab monotherapy period. This occurred in 33 of the 40 patients (83%; 95% confidence interval, 67%-93%; P less than .001); in fact, 60% of patients (n = 24) experienced a decrease of at least 1.0 log₁₀ copies/mL during that period, and the mean and median reductions were 1.1 log₁₀ copies/mL. One secondary end point was increase in CD4 counts: The mean increase was 62 cells/mcL, although smaller increases were seen among patients with lower starting counts. Of the 10 patients who exhibited virologic failure or rebound, 9 showed less susceptibility to ibalizumab at week 25 than they had shown at baseline.

At least one adverse event was seen in 32 patients (80%), although most (87%) of those events were mild to moderate in severity, such as diarrhea (20%) and nausea, fatigue, pyrexia, rash, and dizziness (13% each). More serious events (grade 3 or 4) were seen in 28% of patients (n = 11); serious events were seen in nine patients – including immune reconstitution inflammatory syndrome in one. Four patients died during the study, although none of the deaths were believed to have been related to treatment with ibalizumab.

The investigators noted that the study’s limitations – its small size, uncontrolled design, and limited time for analyzing secondary and safety endpoints – were largely related to small number of patients with MDR HIV-1. The investigators noted that, in accordance with HIV treatment guidelines, patients who experience resistance-related treatment failure should be started on a regimen that includes at least two fully active agents; the investigators suggest that the addition of a drug like ibalizumab provides new opportunities for effective treatments in these situations.

This study was originally presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The study was supported by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed, which developed ibalizumab. The authors disclosed ties to various industry entities, including grants, personal fees, nonfinancial support, and other forms of support from TaiMed.

[email protected]

SOURCE: Emu B et al. New Engl J Med. 2018 Aug 16;379(9):645-54.

In combination with an optimized background regimen, the humanized IgG4 monoclonal antibody ibalizumab can reduce viral load and increase CD4 counts in patients with multidrug-resistant HIV type 1 (MDR HIV-1), according to a study published in the New England Journal of Medicine. It does so by binding noncompetitively to CD4 receptors, which can thereby block HIV-1 entry.

copyright alexskopje/Thinkstock

TMB-301 (NCT02475629) was a 24-week, open-label, single-group, phase 3 study that included patients with MDR HIV-1. During July 2015 to October 2016, patients first continued on their previous treatment for 7 days, then were given a 2,000-mg loading dose of ibalizumab as monotherapy, and then continued on 800 mg ibalizumab every 14 days plus an individualized regimen that was optimized based on patients’ past treatments for the remainder of the study period.

The primary endpoint was how many patients experienced a decrease in viral load of at least 0.5 log₁₀ copies/mL from baseline to day 14 – that is, after the 7-day control period plus the 7-days ibalizumab monotherapy period. This occurred in 33 of the 40 patients (83%; 95% confidence interval, 67%-93%; P less than .001); in fact, 60% of patients (n = 24) experienced a decrease of at least 1.0 log₁₀ copies/mL during that period, and the mean and median reductions were 1.1 log₁₀ copies/mL. One secondary end point was increase in CD4 counts: The mean increase was 62 cells/mcL, although smaller increases were seen among patients with lower starting counts. Of the 10 patients who exhibited virologic failure or rebound, 9 showed less susceptibility to ibalizumab at week 25 than they had shown at baseline.

At least one adverse event was seen in 32 patients (80%), although most (87%) of those events were mild to moderate in severity, such as diarrhea (20%) and nausea, fatigue, pyrexia, rash, and dizziness (13% each). More serious events (grade 3 or 4) were seen in 28% of patients (n = 11); serious events were seen in nine patients – including immune reconstitution inflammatory syndrome in one. Four patients died during the study, although none of the deaths were believed to have been related to treatment with ibalizumab.

The investigators noted that the study’s limitations – its small size, uncontrolled design, and limited time for analyzing secondary and safety endpoints – were largely related to small number of patients with MDR HIV-1. The investigators noted that, in accordance with HIV treatment guidelines, patients who experience resistance-related treatment failure should be started on a regimen that includes at least two fully active agents; the investigators suggest that the addition of a drug like ibalizumab provides new opportunities for effective treatments in these situations.

This study was originally presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The study was supported by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed, which developed ibalizumab. The authors disclosed ties to various industry entities, including grants, personal fees, nonfinancial support, and other forms of support from TaiMed.

[email protected]

SOURCE: Emu B et al. New Engl J Med. 2018 Aug 16;379(9):645-54.

In combination with an optimized background regimen, the humanized IgG4 monoclonal antibody ibalizumab can reduce viral load and increase CD4 counts in patients with multidrug-resistant HIV type 1 (MDR HIV-1), according to a study published in the New England Journal of Medicine. It does so by binding noncompetitively to CD4 receptors, which can thereby block HIV-1 entry.

copyright alexskopje/Thinkstock

TMB-301 (NCT02475629) was a 24-week, open-label, single-group, phase 3 study that included patients with MDR HIV-1. During July 2015 to October 2016, patients first continued on their previous treatment for 7 days, then were given a 2,000-mg loading dose of ibalizumab as monotherapy, and then continued on 800 mg ibalizumab every 14 days plus an individualized regimen that was optimized based on patients’ past treatments for the remainder of the study period.

The primary endpoint was how many patients experienced a decrease in viral load of at least 0.5 log₁₀ copies/mL from baseline to day 14 – that is, after the 7-day control period plus the 7-days ibalizumab monotherapy period. This occurred in 33 of the 40 patients (83%; 95% confidence interval, 67%-93%; P less than .001); in fact, 60% of patients (n = 24) experienced a decrease of at least 1.0 log₁₀ copies/mL during that period, and the mean and median reductions were 1.1 log₁₀ copies/mL. One secondary end point was increase in CD4 counts: The mean increase was 62 cells/mcL, although smaller increases were seen among patients with lower starting counts. Of the 10 patients who exhibited virologic failure or rebound, 9 showed less susceptibility to ibalizumab at week 25 than they had shown at baseline.

At least one adverse event was seen in 32 patients (80%), although most (87%) of those events were mild to moderate in severity, such as diarrhea (20%) and nausea, fatigue, pyrexia, rash, and dizziness (13% each). More serious events (grade 3 or 4) were seen in 28% of patients (n = 11); serious events were seen in nine patients – including immune reconstitution inflammatory syndrome in one. Four patients died during the study, although none of the deaths were believed to have been related to treatment with ibalizumab.

The investigators noted that the study’s limitations – its small size, uncontrolled design, and limited time for analyzing secondary and safety endpoints – were largely related to small number of patients with MDR HIV-1. The investigators noted that, in accordance with HIV treatment guidelines, patients who experience resistance-related treatment failure should be started on a regimen that includes at least two fully active agents; the investigators suggest that the addition of a drug like ibalizumab provides new opportunities for effective treatments in these situations.

This study was originally presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The study was supported by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed, which developed ibalizumab. The authors disclosed ties to various industry entities, including grants, personal fees, nonfinancial support, and other forms of support from TaiMed.

[email protected]

SOURCE: Emu B et al. New Engl J Med. 2018 Aug 16;379(9):645-54.

Taking steps to manage cardiovascular risk can help improve long-term outcomes for type 2 diabetes mellitus, according to two new studies published Aug. 16 in the New England Journal of Medicine.

The first study, which examined weight gain after smoking cessation, found that despite a temporary increase in T2DM risk, post-cessation weight gain did not diminish the long-term benefits of reduced cardiovascular and all-cause mortality.

The analysis included three cohort studies: the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS II), and the Health Professionals Follow-Up Study (HPFS), with follow-up questionnaires every 2 years. After exclusions, a total of 162,807 patients were included in the diabetes analysis and 170,723 in the mortality analysis, reported Yang Hu of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626).

In each follow-up cycle, participants who reported being smokers in the previous cycle but “past” smokers in the current cycle were identified. Quitters were defined as either transient quitters (past smokers in the current cycle but current smokers in previous and next cycles), recent quitters (2-6 consecutive years since smoking cessation), and long-term quitters (6 or more consecutive years since cessation). Weight change was observed for the first 6 years after quitting.

Overall, 12,384 cases of T2DM were confirmed. Diabetes risk was higher for recent quitters than for current smokers (hazard ratio, 1.22; 95% confidence interval, 1.12-1.32); this risk peaked 5-7 years after quitting and then gradually decreased. In analysis of patients with the longest follow-up time, diabetes risk dropped after 30 years of cessation to that of participants who had never smoked, the authors reported.

Compared with current smokers, hazard ratios for T2DM in recent quitters were 1.08 (95% CI, 0.93-1.26) for those without weight gain, 1.15 (95% CI, 0.99-1.33) for those with weight gain of 0.1-5.0 kg, 1.36 (95% CI, 1.16-1.58) for those with weight gain of 5.1-10 kg, and 1.59 (95% CI, 1.36-1.85) in those with weight gain of more than 10 kg.

In the mortality analysis, 23,867 deaths occurred, of which 5,492 were due to cardiovascular disease. Compared with current smokers, hazard ratios for death from cardiovascular disease in recent quitters were 0.69 (95% CI, 0.54-0.88) in those without weight gain; 0.47 (95% CI, 0.35-0.63) in those with weight gain of 0.1-5 kg; 0.25 (95% CI, 0.15-0.42) in those with weight gain of 5.1-10 kg; 0.33 (95% CI, 0.18-0.60) in those with weight gain of more than 10 kg; and 0.50 (95% CI, 0.46-0.55) for longer term quitters. The corresponding hazard ratios for all-cause deaths in the same weight gain groups were 0.81 (95% CI, 0.73-0.90); 0.52 (95% CI, 0.46-0.59); 0.46 (95% CI, 0.38-0.55); 0.50 (95% CI, 0.40-0.63); and 0.57 (95% CI, 0.54-0.59).

The findings suggest that weight gain after quitting smoking “did not attenuate the apparent benefits of smoking cessation on reducing cardiovascular mortality or extending longevity,” the authors said. “However, preventing excessive weight gain may maximize the health benefits of smoking cessation through reducing the short-term risk of diabetes and further lowering the long-term risk of death.”

The second study, which included 271,174 patients with T2DM from the Swedish National Diabetes Register and 1,355,870 controls, examined five risk factors: elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure.

All-cause mortality, myocardial infarction, stroke, and hospitalization for heart failure were evaluated. The risk of each outcome among patients with T2DM was estimated according to the number of risk-factor variables within guideline-recommended target ranges, compared with matched controls, wrote Aidin Rawshani, MD, of the department of molecular and clinical medicine at the University of Gothenburg (Sweden), and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256).

Among the T2DM patients, the excess risk of outcomes was reduced with each risk factor variable within the recommended target range. A total of 37,825 patients with T2DM (13.9%) and 137,520 controls (10.1%) died during the study period.

Among T2DM patients with all variables within target range, the hazard ratio was 1.06 for all-cause death (95% CI, 1.00-1.12); 0.84 for acute myocardial infarction (95% CI, 0.75-0.93); and 0.95 for stroke (95% CI, 0.84-1.07). Smoking was the strongest predictor of death, followed by physical activity, marital status, glycated hemoglobin level, and use of statins.

The study results “indicate that having all five risk-factor variables within the target ranges could theoretically eliminate the excess risk of acute myocardial infarction,” Dr. Rawshani and his colleagues wrote. “Patients with type 2 diabetes who had five risk-factor variables within target ranges appeared to have little or no excess risks of death, myocardial infarction, and stroke as compared with the general population.”

Dr. Hu and his coauthors did not report any disclosures. Dr. Rawshani’s coauthors disclosed relationships with numerous companies including Amgen, Astra Zeneca, and Boehringer Ingelheim.

SOURCE: Hu Y et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626. Rawshani A et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256.

Taking steps to manage cardiovascular risk can help improve long-term outcomes for type 2 diabetes mellitus, according to two new studies published Aug. 16 in the New England Journal of Medicine.

The first study, which examined weight gain after smoking cessation, found that despite a temporary increase in T2DM risk, post-cessation weight gain did not diminish the long-term benefits of reduced cardiovascular and all-cause mortality.

The analysis included three cohort studies: the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS II), and the Health Professionals Follow-Up Study (HPFS), with follow-up questionnaires every 2 years. After exclusions, a total of 162,807 patients were included in the diabetes analysis and 170,723 in the mortality analysis, reported Yang Hu of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626).

In each follow-up cycle, participants who reported being smokers in the previous cycle but “past” smokers in the current cycle were identified. Quitters were defined as either transient quitters (past smokers in the current cycle but current smokers in previous and next cycles), recent quitters (2-6 consecutive years since smoking cessation), and long-term quitters (6 or more consecutive years since cessation). Weight change was observed for the first 6 years after quitting.

Overall, 12,384 cases of T2DM were confirmed. Diabetes risk was higher for recent quitters than for current smokers (hazard ratio, 1.22; 95% confidence interval, 1.12-1.32); this risk peaked 5-7 years after quitting and then gradually decreased. In analysis of patients with the longest follow-up time, diabetes risk dropped after 30 years of cessation to that of participants who had never smoked, the authors reported.

Compared with current smokers, hazard ratios for T2DM in recent quitters were 1.08 (95% CI, 0.93-1.26) for those without weight gain, 1.15 (95% CI, 0.99-1.33) for those with weight gain of 0.1-5.0 kg, 1.36 (95% CI, 1.16-1.58) for those with weight gain of 5.1-10 kg, and 1.59 (95% CI, 1.36-1.85) in those with weight gain of more than 10 kg.

In the mortality analysis, 23,867 deaths occurred, of which 5,492 were due to cardiovascular disease. Compared with current smokers, hazard ratios for death from cardiovascular disease in recent quitters were 0.69 (95% CI, 0.54-0.88) in those without weight gain; 0.47 (95% CI, 0.35-0.63) in those with weight gain of 0.1-5 kg; 0.25 (95% CI, 0.15-0.42) in those with weight gain of 5.1-10 kg; 0.33 (95% CI, 0.18-0.60) in those with weight gain of more than 10 kg; and 0.50 (95% CI, 0.46-0.55) for longer term quitters. The corresponding hazard ratios for all-cause deaths in the same weight gain groups were 0.81 (95% CI, 0.73-0.90); 0.52 (95% CI, 0.46-0.59); 0.46 (95% CI, 0.38-0.55); 0.50 (95% CI, 0.40-0.63); and 0.57 (95% CI, 0.54-0.59).

The findings suggest that weight gain after quitting smoking “did not attenuate the apparent benefits of smoking cessation on reducing cardiovascular mortality or extending longevity,” the authors said. “However, preventing excessive weight gain may maximize the health benefits of smoking cessation through reducing the short-term risk of diabetes and further lowering the long-term risk of death.”

The second study, which included 271,174 patients with T2DM from the Swedish National Diabetes Register and 1,355,870 controls, examined five risk factors: elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure.

All-cause mortality, myocardial infarction, stroke, and hospitalization for heart failure were evaluated. The risk of each outcome among patients with T2DM was estimated according to the number of risk-factor variables within guideline-recommended target ranges, compared with matched controls, wrote Aidin Rawshani, MD, of the department of molecular and clinical medicine at the University of Gothenburg (Sweden), and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256).

Among the T2DM patients, the excess risk of outcomes was reduced with each risk factor variable within the recommended target range. A total of 37,825 patients with T2DM (13.9%) and 137,520 controls (10.1%) died during the study period.

Among T2DM patients with all variables within target range, the hazard ratio was 1.06 for all-cause death (95% CI, 1.00-1.12); 0.84 for acute myocardial infarction (95% CI, 0.75-0.93); and 0.95 for stroke (95% CI, 0.84-1.07). Smoking was the strongest predictor of death, followed by physical activity, marital status, glycated hemoglobin level, and use of statins.

The study results “indicate that having all five risk-factor variables within the target ranges could theoretically eliminate the excess risk of acute myocardial infarction,” Dr. Rawshani and his colleagues wrote. “Patients with type 2 diabetes who had five risk-factor variables within target ranges appeared to have little or no excess risks of death, myocardial infarction, and stroke as compared with the general population.”

Dr. Hu and his coauthors did not report any disclosures. Dr. Rawshani’s coauthors disclosed relationships with numerous companies including Amgen, Astra Zeneca, and Boehringer Ingelheim.

SOURCE: Hu Y et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626. Rawshani A et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256.

Taking steps to manage cardiovascular risk can help improve long-term outcomes for type 2 diabetes mellitus, according to two new studies published Aug. 16 in the New England Journal of Medicine.

The first study, which examined weight gain after smoking cessation, found that despite a temporary increase in T2DM risk, post-cessation weight gain did not diminish the long-term benefits of reduced cardiovascular and all-cause mortality.

The analysis included three cohort studies: the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS II), and the Health Professionals Follow-Up Study (HPFS), with follow-up questionnaires every 2 years. After exclusions, a total of 162,807 patients were included in the diabetes analysis and 170,723 in the mortality analysis, reported Yang Hu of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626).

In each follow-up cycle, participants who reported being smokers in the previous cycle but “past” smokers in the current cycle were identified. Quitters were defined as either transient quitters (past smokers in the current cycle but current smokers in previous and next cycles), recent quitters (2-6 consecutive years since smoking cessation), and long-term quitters (6 or more consecutive years since cessation). Weight change was observed for the first 6 years after quitting.

Overall, 12,384 cases of T2DM were confirmed. Diabetes risk was higher for recent quitters than for current smokers (hazard ratio, 1.22; 95% confidence interval, 1.12-1.32); this risk peaked 5-7 years after quitting and then gradually decreased. In analysis of patients with the longest follow-up time, diabetes risk dropped after 30 years of cessation to that of participants who had never smoked, the authors reported.

Compared with current smokers, hazard ratios for T2DM in recent quitters were 1.08 (95% CI, 0.93-1.26) for those without weight gain, 1.15 (95% CI, 0.99-1.33) for those with weight gain of 0.1-5.0 kg, 1.36 (95% CI, 1.16-1.58) for those with weight gain of 5.1-10 kg, and 1.59 (95% CI, 1.36-1.85) in those with weight gain of more than 10 kg.

In the mortality analysis, 23,867 deaths occurred, of which 5,492 were due to cardiovascular disease. Compared with current smokers, hazard ratios for death from cardiovascular disease in recent quitters were 0.69 (95% CI, 0.54-0.88) in those without weight gain; 0.47 (95% CI, 0.35-0.63) in those with weight gain of 0.1-5 kg; 0.25 (95% CI, 0.15-0.42) in those with weight gain of 5.1-10 kg; 0.33 (95% CI, 0.18-0.60) in those with weight gain of more than 10 kg; and 0.50 (95% CI, 0.46-0.55) for longer term quitters. The corresponding hazard ratios for all-cause deaths in the same weight gain groups were 0.81 (95% CI, 0.73-0.90); 0.52 (95% CI, 0.46-0.59); 0.46 (95% CI, 0.38-0.55); 0.50 (95% CI, 0.40-0.63); and 0.57 (95% CI, 0.54-0.59).

The findings suggest that weight gain after quitting smoking “did not attenuate the apparent benefits of smoking cessation on reducing cardiovascular mortality or extending longevity,” the authors said. “However, preventing excessive weight gain may maximize the health benefits of smoking cessation through reducing the short-term risk of diabetes and further lowering the long-term risk of death.”

The second study, which included 271,174 patients with T2DM from the Swedish National Diabetes Register and 1,355,870 controls, examined five risk factors: elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure.

All-cause mortality, myocardial infarction, stroke, and hospitalization for heart failure were evaluated. The risk of each outcome among patients with T2DM was estimated according to the number of risk-factor variables within guideline-recommended target ranges, compared with matched controls, wrote Aidin Rawshani, MD, of the department of molecular and clinical medicine at the University of Gothenburg (Sweden), and his coauthors (N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256).

Among the T2DM patients, the excess risk of outcomes was reduced with each risk factor variable within the recommended target range. A total of 37,825 patients with T2DM (13.9%) and 137,520 controls (10.1%) died during the study period.

Among T2DM patients with all variables within target range, the hazard ratio was 1.06 for all-cause death (95% CI, 1.00-1.12); 0.84 for acute myocardial infarction (95% CI, 0.75-0.93); and 0.95 for stroke (95% CI, 0.84-1.07). Smoking was the strongest predictor of death, followed by physical activity, marital status, glycated hemoglobin level, and use of statins.

The study results “indicate that having all five risk-factor variables within the target ranges could theoretically eliminate the excess risk of acute myocardial infarction,” Dr. Rawshani and his colleagues wrote. “Patients with type 2 diabetes who had five risk-factor variables within target ranges appeared to have little or no excess risks of death, myocardial infarction, and stroke as compared with the general population.”

Dr. Hu and his coauthors did not report any disclosures. Dr. Rawshani’s coauthors disclosed relationships with numerous companies including Amgen, Astra Zeneca, and Boehringer Ingelheim.

SOURCE: Hu Y et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1803626. Rawshani A et al. N Engl J Med. 2018 Aug 16. doi: 10.1056/NEJMoa1800256.

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

Exercise is good for the body and can be beneficial for the mind. But when it comes to the type of activity, the quality of the sweat might vary from mundane to wonderful depending on your personality.

shironosov/Thinkstock

“People tend to think that there’s one best way to go about an exercise routine, but one-size-fits-all doesn’t apply here. Instead, it’s important to know who you are and select a type of exercise that fits,” said John Hackston, a psychologist with the British firm OPP, which markets personality assessment programs and business psychology solutions. He also led a study presented at the last meeting of the British Psychological Society.

“We were keen to investigate how organizations could help their staffs’ development through exercise, finding that matching an individual’s personality type to a particular type of exercise can increase both the effectiveness and the person’s enjoyment of it,” he explained in an interview with Science Daily.

The survey of more than 800 people from diverse businesses in several countries showed that certain exercise activities and settings attract certain personalities.

Extroverts might prefer the hustle bustle of a health club, where group exercise classes and rows of equipment provide the opportunity for the shedding of sweat in a social setting and can offer the group motivation to keep the exercise going. By contrast, introverts might prefer the rejuvenating peace and solitude of a long-distance run or walk.

The findings went further. Regimented exercise was appealing to those whose outlook on the world was through the lens of objective logic, but not those who place more importance on feelings and values.

The changing nature of the outdoors attracted people with a more creative mindset, particularly those open to new ideas. For these folks, outdoor activities like running and cycling fit the bill better than the local gym.

“The most important piece of advice to come out of this research is that there is not one type of exercise that is suited to everyone, ” Mr. Hackston said. “There can be pressure to follow the crowd to the gym or sign up to the latest exercise fad, but it would be much more effective for them to match their personality type to an exercise plan that is more likely to last the test of time.”

Click here to read about the study.

Exercise is good for the body and can be beneficial for the mind. But when it comes to the type of activity, the quality of the sweat might vary from mundane to wonderful depending on your personality.

shironosov/Thinkstock

“People tend to think that there’s one best way to go about an exercise routine, but one-size-fits-all doesn’t apply here. Instead, it’s important to know who you are and select a type of exercise that fits,” said John Hackston, a psychologist with the British firm OPP, which markets personality assessment programs and business psychology solutions. He also led a study presented at the last meeting of the British Psychological Society.

“We were keen to investigate how organizations could help their staffs’ development through exercise, finding that matching an individual’s personality type to a particular type of exercise can increase both the effectiveness and the person’s enjoyment of it,” he explained in an interview with Science Daily.

The survey of more than 800 people from diverse businesses in several countries showed that certain exercise activities and settings attract certain personalities.

Extroverts might prefer the hustle bustle of a health club, where group exercise classes and rows of equipment provide the opportunity for the shedding of sweat in a social setting and can offer the group motivation to keep the exercise going. By contrast, introverts might prefer the rejuvenating peace and solitude of a long-distance run or walk.

The findings went further. Regimented exercise was appealing to those whose outlook on the world was through the lens of objective logic, but not those who place more importance on feelings and values.

The changing nature of the outdoors attracted people with a more creative mindset, particularly those open to new ideas. For these folks, outdoor activities like running and cycling fit the bill better than the local gym.

“The most important piece of advice to come out of this research is that there is not one type of exercise that is suited to everyone, ” Mr. Hackston said. “There can be pressure to follow the crowd to the gym or sign up to the latest exercise fad, but it would be much more effective for them to match their personality type to an exercise plan that is more likely to last the test of time.”

Click here to read about the study.

Exercise is good for the body and can be beneficial for the mind. But when it comes to the type of activity, the quality of the sweat might vary from mundane to wonderful depending on your personality.

shironosov/Thinkstock

“People tend to think that there’s one best way to go about an exercise routine, but one-size-fits-all doesn’t apply here. Instead, it’s important to know who you are and select a type of exercise that fits,” said John Hackston, a psychologist with the British firm OPP, which markets personality assessment programs and business psychology solutions. He also led a study presented at the last meeting of the British Psychological Society.

“We were keen to investigate how organizations could help their staffs’ development through exercise, finding that matching an individual’s personality type to a particular type of exercise can increase both the effectiveness and the person’s enjoyment of it,” he explained in an interview with Science Daily.

The survey of more than 800 people from diverse businesses in several countries showed that certain exercise activities and settings attract certain personalities.

Extroverts might prefer the hustle bustle of a health club, where group exercise classes and rows of equipment provide the opportunity for the shedding of sweat in a social setting and can offer the group motivation to keep the exercise going. By contrast, introverts might prefer the rejuvenating peace and solitude of a long-distance run or walk.

The findings went further. Regimented exercise was appealing to those whose outlook on the world was through the lens of objective logic, but not those who place more importance on feelings and values.

The changing nature of the outdoors attracted people with a more creative mindset, particularly those open to new ideas. For these folks, outdoor activities like running and cycling fit the bill better than the local gym.

“The most important piece of advice to come out of this research is that there is not one type of exercise that is suited to everyone, ” Mr. Hackston said. “There can be pressure to follow the crowd to the gym or sign up to the latest exercise fad, but it would be much more effective for them to match their personality type to an exercise plan that is more likely to last the test of time.”

Click here to read about the study.

ROCKVILLE, MD. – Using a digital application could allow more adults to try cognitive-behavioral therapy (CBT) to combat insomnia and expand access to a technique that’s been shown to ward off depression, a researcher said at a National Institute of Mental Health conference on mental health services research.

ROCKVILLE, MD. – Using a digital application could allow more adults to try cognitive-behavioral therapy (CBT) to combat insomnia and expand access to a technique that’s been shown to ward off depression, a researcher said at a National Institute of Mental Health conference on mental health services research.

ROCKVILLE, MD. – Using a digital application could allow more adults to try cognitive-behavioral therapy (CBT) to combat insomnia and expand access to a technique that’s been shown to ward off depression, a researcher said at a National Institute of Mental Health conference on mental health services research.

People with systemic lupus erythematosus (SLE) taking antimalarials, particularly for prolonged periods, could be at risk for cardiomyopathy, and measuring specific myocardial biomarkers could help identify patients at particularly high risk, researchers have suggested.

Writing in the Journal of Rheumatology, the research team led by Konstantinos Tselios, MD, PhD, of the University of Toronto Lupus Clinic at the Centre for Prognosis Studies in the Rheumatic Diseases, noted that antimalarial-induced cardiomyopathy (AMIC) had been reported in 47 patients to date, 19 of whom had SLE, with duration and cumulative use of antimalarials thought to be the cause.

The authors suggested that AMIC could be underrecognized because antimalarials were currently recommended for all patients with SLE (without known contraindications) for prolonged periods. It was speculated that the mechanism by which AMIC occurred involved the deposition of antimalarials in the myocardial fibers and that this could lead to chronic, subclinical tissue necrosis, a process which, if not reversed, could lead to heart failure.

“Heart-specific biomarkers, such as cardiac troponin (for the assessment of myocardial necrosis) and brain natriuretic peptide (BNP; for the assessment of volume and/or pressure overload), may be of value in identifying subclinical heart damage,” the research team suggested.

The current study involved 151 consecutive patients with SLE who had no prior cardiac disease and were attending the University of Toronto Lupus Clinic from March to May 2016.

During the course of the disease, 28 of the patients had been taking chloroquine, and 137 had been taking hydroxychloroquine (14 patients had been treated with both drugs at different time periods). In the study, normal range was less than 26 ng/mL for high-sensitivity cardiac troponin I (cTnI) and less than 100 pg/mL for BNP.

Overall, 16 patients (10.6%) had abnormal BNP, of whom 9 (6%) also had abnormal cTnI. Prolonged antimalarial use (greater than 5.6 yrs) was associated with increased risk for these elevated biomarkers, regardless of age and SLE disease duration.

“Because duration of AM [antimalarial] treatment is the critical predictor of AMIC, the majority of patients with SLE should be considered at risk because most of them receive long-term maintenance therapy,” the researchers wrote.

They said that elevations of the biomarkers implicated possible active myocardial necrosis (elevated cTnI) and/or increased intracardiac ventricular pressure (elevated BNP).

“In this context, AM deposition in the myocardium, leading over time to overt cardiomyopathy, may be an important contributing factor. Indeed, 6 out of 16 of these patients were ultimately diagnosed with definite or possible AMIC, while 3 of them were completely asymptomatic, and their investigation was initiated because of the abnormal biomarkers,” they wrote.

The researchers also found that persistent creatine phosphokinase (CPK) elevation was also an important predictor for elevated cardiac biomarkers.

“We showed that chronic AM use is associated with a more than threefold increased risk for elevated CPK (after excluding patients with active myositis and statin therapy). ... It is not known whether elevated CPK may predict patients at risk for development of AMIC or whether certain patients are predisposed to AM-related muscle damage,” they said.

“Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC,” they concluded.

Nevertheless, the authors acknowledged that expensive and invasive investigation was unjustified in asymptomatic individuals. They therefore suggested that identifying heart-specific biomarkers for the detection of subclinical heart damage could allow patients to be stratified according to their risk.

“Cardiac biomarkers could become a screening test for patients with SLE using AM for longer than 5.6 years and/or who have persistently elevated CPK levels. Further research is needed to delineate the differential toxicity of CQ [chloroquine] and HCQ [hydroxychloroquine],” they suggested.

The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario. Dr. Tselios is financially supported by Lupus Ontario.

SOURCE: Tselios K et al. J Rheumatol. 2018. doi: 10.3899/jrheum.171436.

People with systemic lupus erythematosus (SLE) taking antimalarials, particularly for prolonged periods, could be at risk for cardiomyopathy, and measuring specific myocardial biomarkers could help identify patients at particularly high risk, researchers have suggested.

Writing in the Journal of Rheumatology, the research team led by Konstantinos Tselios, MD, PhD, of the University of Toronto Lupus Clinic at the Centre for Prognosis Studies in the Rheumatic Diseases, noted that antimalarial-induced cardiomyopathy (AMIC) had been reported in 47 patients to date, 19 of whom had SLE, with duration and cumulative use of antimalarials thought to be the cause.

The authors suggested that AMIC could be underrecognized because antimalarials were currently recommended for all patients with SLE (without known contraindications) for prolonged periods. It was speculated that the mechanism by which AMIC occurred involved the deposition of antimalarials in the myocardial fibers and that this could lead to chronic, subclinical tissue necrosis, a process which, if not reversed, could lead to heart failure.

“Heart-specific biomarkers, such as cardiac troponin (for the assessment of myocardial necrosis) and brain natriuretic peptide (BNP; for the assessment of volume and/or pressure overload), may be of value in identifying subclinical heart damage,” the research team suggested.

The current study involved 151 consecutive patients with SLE who had no prior cardiac disease and were attending the University of Toronto Lupus Clinic from March to May 2016.

During the course of the disease, 28 of the patients had been taking chloroquine, and 137 had been taking hydroxychloroquine (14 patients had been treated with both drugs at different time periods). In the study, normal range was less than 26 ng/mL for high-sensitivity cardiac troponin I (cTnI) and less than 100 pg/mL for BNP.

Overall, 16 patients (10.6%) had abnormal BNP, of whom 9 (6%) also had abnormal cTnI. Prolonged antimalarial use (greater than 5.6 yrs) was associated with increased risk for these elevated biomarkers, regardless of age and SLE disease duration.

“Because duration of AM [antimalarial] treatment is the critical predictor of AMIC, the majority of patients with SLE should be considered at risk because most of them receive long-term maintenance therapy,” the researchers wrote.

They said that elevations of the biomarkers implicated possible active myocardial necrosis (elevated cTnI) and/or increased intracardiac ventricular pressure (elevated BNP).

“In this context, AM deposition in the myocardium, leading over time to overt cardiomyopathy, may be an important contributing factor. Indeed, 6 out of 16 of these patients were ultimately diagnosed with definite or possible AMIC, while 3 of them were completely asymptomatic, and their investigation was initiated because of the abnormal biomarkers,” they wrote.

The researchers also found that persistent creatine phosphokinase (CPK) elevation was also an important predictor for elevated cardiac biomarkers.

“We showed that chronic AM use is associated with a more than threefold increased risk for elevated CPK (after excluding patients with active myositis and statin therapy). ... It is not known whether elevated CPK may predict patients at risk for development of AMIC or whether certain patients are predisposed to AM-related muscle damage,” they said.

“Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC,” they concluded.

Nevertheless, the authors acknowledged that expensive and invasive investigation was unjustified in asymptomatic individuals. They therefore suggested that identifying heart-specific biomarkers for the detection of subclinical heart damage could allow patients to be stratified according to their risk.

“Cardiac biomarkers could become a screening test for patients with SLE using AM for longer than 5.6 years and/or who have persistently elevated CPK levels. Further research is needed to delineate the differential toxicity of CQ [chloroquine] and HCQ [hydroxychloroquine],” they suggested.

The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario. Dr. Tselios is financially supported by Lupus Ontario.

SOURCE: Tselios K et al. J Rheumatol. 2018. doi: 10.3899/jrheum.171436.

People with systemic lupus erythematosus (SLE) taking antimalarials, particularly for prolonged periods, could be at risk for cardiomyopathy, and measuring specific myocardial biomarkers could help identify patients at particularly high risk, researchers have suggested.

Writing in the Journal of Rheumatology, the research team led by Konstantinos Tselios, MD, PhD, of the University of Toronto Lupus Clinic at the Centre for Prognosis Studies in the Rheumatic Diseases, noted that antimalarial-induced cardiomyopathy (AMIC) had been reported in 47 patients to date, 19 of whom had SLE, with duration and cumulative use of antimalarials thought to be the cause.

The authors suggested that AMIC could be underrecognized because antimalarials were currently recommended for all patients with SLE (without known contraindications) for prolonged periods. It was speculated that the mechanism by which AMIC occurred involved the deposition of antimalarials in the myocardial fibers and that this could lead to chronic, subclinical tissue necrosis, a process which, if not reversed, could lead to heart failure.

“Heart-specific biomarkers, such as cardiac troponin (for the assessment of myocardial necrosis) and brain natriuretic peptide (BNP; for the assessment of volume and/or pressure overload), may be of value in identifying subclinical heart damage,” the research team suggested.

The current study involved 151 consecutive patients with SLE who had no prior cardiac disease and were attending the University of Toronto Lupus Clinic from March to May 2016.

During the course of the disease, 28 of the patients had been taking chloroquine, and 137 had been taking hydroxychloroquine (14 patients had been treated with both drugs at different time periods). In the study, normal range was less than 26 ng/mL for high-sensitivity cardiac troponin I (cTnI) and less than 100 pg/mL for BNP.

Overall, 16 patients (10.6%) had abnormal BNP, of whom 9 (6%) also had abnormal cTnI. Prolonged antimalarial use (greater than 5.6 yrs) was associated with increased risk for these elevated biomarkers, regardless of age and SLE disease duration.

“Because duration of AM [antimalarial] treatment is the critical predictor of AMIC, the majority of patients with SLE should be considered at risk because most of them receive long-term maintenance therapy,” the researchers wrote.

They said that elevations of the biomarkers implicated possible active myocardial necrosis (elevated cTnI) and/or increased intracardiac ventricular pressure (elevated BNP).

“In this context, AM deposition in the myocardium, leading over time to overt cardiomyopathy, may be an important contributing factor. Indeed, 6 out of 16 of these patients were ultimately diagnosed with definite or possible AMIC, while 3 of them were completely asymptomatic, and their investigation was initiated because of the abnormal biomarkers,” they wrote.

The researchers also found that persistent creatine phosphokinase (CPK) elevation was also an important predictor for elevated cardiac biomarkers.

“We showed that chronic AM use is associated with a more than threefold increased risk for elevated CPK (after excluding patients with active myositis and statin therapy). ... It is not known whether elevated CPK may predict patients at risk for development of AMIC or whether certain patients are predisposed to AM-related muscle damage,” they said.

“Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC,” they concluded.

Nevertheless, the authors acknowledged that expensive and invasive investigation was unjustified in asymptomatic individuals. They therefore suggested that identifying heart-specific biomarkers for the detection of subclinical heart damage could allow patients to be stratified according to their risk.

“Cardiac biomarkers could become a screening test for patients with SLE using AM for longer than 5.6 years and/or who have persistently elevated CPK levels. Further research is needed to delineate the differential toxicity of CQ [chloroquine] and HCQ [hydroxychloroquine],” they suggested.

The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario. Dr. Tselios is financially supported by Lupus Ontario.

SOURCE: Tselios K et al. J Rheumatol. 2018. doi: 10.3899/jrheum.171436.