Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons

The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.

 

Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons

The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.

 

Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons

The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.

 

Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

 

PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.

Bruce Jancin/MDedge News

Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.

PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.

Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
 

Primary and secondary outcomes

One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.

Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.

The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.

The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.

Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.

One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”

“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”

Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.

[email protected]

 

PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.

Bruce Jancin/MDedge News

Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.

PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.

Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
 

Primary and secondary outcomes

One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.

Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.

The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.

The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.

Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.

One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”

“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”

Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.

[email protected]

 

PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.

Bruce Jancin/MDedge News

Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.

PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.

Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
 

Primary and secondary outcomes

One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.

Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.

The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.

The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.

Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.

One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”

“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”

Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.

[email protected]

 

SAN DIEGO – The United States is more ethnically diverse than ever before, creating an added challenge for dermatologists to identify skin types in patients considering aesthetic procedures.

“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”

When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”

He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”

In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.

“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”

To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”

Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”

Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.

Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.

As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.

“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”

Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.

[email protected]

 

SAN DIEGO – The United States is more ethnically diverse than ever before, creating an added challenge for dermatologists to identify skin types in patients considering aesthetic procedures.

“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”

When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”

He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”

In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.

“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”

To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”

Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”

Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.

Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.

As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.

“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”

Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.

[email protected]

 

SAN DIEGO – The United States is more ethnically diverse than ever before, creating an added challenge for dermatologists to identify skin types in patients considering aesthetic procedures.

“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”

When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”

He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”

In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.

“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”

To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”

Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”

Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.

Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.

As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.

“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”

Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.

[email protected]