WASHINGTON – Therapy targeting early maladaptive schemas can reduce the severity of PTSD symptoms and improve the quality of life for patients, according to data presented at the annual conference of the Anxiety and Depression Association of America.

Change in early maladaptive schemas correlated with a 13%-20% variation in PTSD symptom severity among patients tested, which points to the efficacy of incorporating schema-based interventions in trauma-focused therapies, said Karina T. Loyo, of Marquette University, Milwaukee.

Early maladaptive schemas, broad worldviews that develop in childhood, can lead to unhealthy, pervasive expectations in adulthood that directly inhibit PTSD treatment, according to Ms. Loyo. “We can see with how early maladaptive schemas developed early on can influence how an individual interprets a traumatic event,” she said.

To test whether early maladaptive schemas can predict symptom reduction and life improvement beyond trauma-related cognitions, Ms. Loyo and her colleagues gave 120 PTSD patients an early maladaptive schemas questionnaire, a quality of life questionnaire, as well as the Posttraumatic Cognitions Inventory.

Using a regression model, investigators found the Posttraumatic Cognitions Inventory and schema questionnaire predicted quality of life fairly accurately. This was especially true of the schema questionnaire, which predicted 20% more variance in quality of life scores, Ms. Loyo said.

“This suggests that schema-focused therapy [SFT] is related to PTSD symptom severity reduction,” Ms. Loyo said. “This has clinical implications as far as how we integrate schema-based interventions in trauma-focused areas.”

These schema-based treatments can be used to change a patient’s thoughts on their disorder, as well as gather information. For example, a patient exhibiting the early maladaptive schema of mistrust from abuse might be suspicious of others based on childhood experiences of being used or taken advantage of by others. This can lead to alienation from others, which in turn, would affect the patient’s quality of life after their traumatic experience.

Using SFT, clinicians can talk through and identify the possible intentions of those in the patient’s life to reinforce the notion that the people in their life might be both imperfect yet trustworthy, Ms. Loyo said.

SFT can also be used to address childhood trauma that caused a patient’s development of early maladaptive schemas. This kind of work can build trust between the clinician and the patient – and make subsequent treatments more effective.

Unlike a typical trauma narrative, SFT focuses on increasing awareness of patients’ emotions before the trauma occurred and how they felt while addressing the moment the trauma occurred. In addition, SFT uses a slightly different form of imagery scripting in an effort to acknowledge patients’ pain and direct them in a more constructive direction to channel those emotions into rebuilding values such as trust.

Ms. Loyo reported no financial disclosures.

[email protected]

SOURCE: Loyo KT et al. ADAA 2018.

WASHINGTON – Therapy targeting early maladaptive schemas can reduce the severity of PTSD symptoms and improve the quality of life for patients, according to data presented at the annual conference of the Anxiety and Depression Association of America.

Change in early maladaptive schemas correlated with a 13%-20% variation in PTSD symptom severity among patients tested, which points to the efficacy of incorporating schema-based interventions in trauma-focused therapies, said Karina T. Loyo, of Marquette University, Milwaukee.

Early maladaptive schemas, broad worldviews that develop in childhood, can lead to unhealthy, pervasive expectations in adulthood that directly inhibit PTSD treatment, according to Ms. Loyo. “We can see with how early maladaptive schemas developed early on can influence how an individual interprets a traumatic event,” she said.

To test whether early maladaptive schemas can predict symptom reduction and life improvement beyond trauma-related cognitions, Ms. Loyo and her colleagues gave 120 PTSD patients an early maladaptive schemas questionnaire, a quality of life questionnaire, as well as the Posttraumatic Cognitions Inventory.

Using a regression model, investigators found the Posttraumatic Cognitions Inventory and schema questionnaire predicted quality of life fairly accurately. This was especially true of the schema questionnaire, which predicted 20% more variance in quality of life scores, Ms. Loyo said.

“This suggests that schema-focused therapy [SFT] is related to PTSD symptom severity reduction,” Ms. Loyo said. “This has clinical implications as far as how we integrate schema-based interventions in trauma-focused areas.”

These schema-based treatments can be used to change a patient’s thoughts on their disorder, as well as gather information. For example, a patient exhibiting the early maladaptive schema of mistrust from abuse might be suspicious of others based on childhood experiences of being used or taken advantage of by others. This can lead to alienation from others, which in turn, would affect the patient’s quality of life after their traumatic experience.

Using SFT, clinicians can talk through and identify the possible intentions of those in the patient’s life to reinforce the notion that the people in their life might be both imperfect yet trustworthy, Ms. Loyo said.

SFT can also be used to address childhood trauma that caused a patient’s development of early maladaptive schemas. This kind of work can build trust between the clinician and the patient – and make subsequent treatments more effective.

Unlike a typical trauma narrative, SFT focuses on increasing awareness of patients’ emotions before the trauma occurred and how they felt while addressing the moment the trauma occurred. In addition, SFT uses a slightly different form of imagery scripting in an effort to acknowledge patients’ pain and direct them in a more constructive direction to channel those emotions into rebuilding values such as trust.

Ms. Loyo reported no financial disclosures.

[email protected]

SOURCE: Loyo KT et al. ADAA 2018.

WASHINGTON – Therapy targeting early maladaptive schemas can reduce the severity of PTSD symptoms and improve the quality of life for patients, according to data presented at the annual conference of the Anxiety and Depression Association of America.

Change in early maladaptive schemas correlated with a 13%-20% variation in PTSD symptom severity among patients tested, which points to the efficacy of incorporating schema-based interventions in trauma-focused therapies, said Karina T. Loyo, of Marquette University, Milwaukee.

Early maladaptive schemas, broad worldviews that develop in childhood, can lead to unhealthy, pervasive expectations in adulthood that directly inhibit PTSD treatment, according to Ms. Loyo. “We can see with how early maladaptive schemas developed early on can influence how an individual interprets a traumatic event,” she said.

To test whether early maladaptive schemas can predict symptom reduction and life improvement beyond trauma-related cognitions, Ms. Loyo and her colleagues gave 120 PTSD patients an early maladaptive schemas questionnaire, a quality of life questionnaire, as well as the Posttraumatic Cognitions Inventory.

Using a regression model, investigators found the Posttraumatic Cognitions Inventory and schema questionnaire predicted quality of life fairly accurately. This was especially true of the schema questionnaire, which predicted 20% more variance in quality of life scores, Ms. Loyo said.

“This suggests that schema-focused therapy [SFT] is related to PTSD symptom severity reduction,” Ms. Loyo said. “This has clinical implications as far as how we integrate schema-based interventions in trauma-focused areas.”

These schema-based treatments can be used to change a patient’s thoughts on their disorder, as well as gather information. For example, a patient exhibiting the early maladaptive schema of mistrust from abuse might be suspicious of others based on childhood experiences of being used or taken advantage of by others. This can lead to alienation from others, which in turn, would affect the patient’s quality of life after their traumatic experience.

Using SFT, clinicians can talk through and identify the possible intentions of those in the patient’s life to reinforce the notion that the people in their life might be both imperfect yet trustworthy, Ms. Loyo said.

SFT can also be used to address childhood trauma that caused a patient’s development of early maladaptive schemas. This kind of work can build trust between the clinician and the patient – and make subsequent treatments more effective.

Unlike a typical trauma narrative, SFT focuses on increasing awareness of patients’ emotions before the trauma occurred and how they felt while addressing the moment the trauma occurred. In addition, SFT uses a slightly different form of imagery scripting in an effort to acknowledge patients’ pain and direct them in a more constructive direction to channel those emotions into rebuilding values such as trust.

Ms. Loyo reported no financial disclosures.

[email protected]

SOURCE: Loyo KT et al. ADAA 2018.

Who’s going to negotiate your contract: you or a professional? Lawyer Scott Roman – at a recent AGA Regional Practice Skills Workshop – explained that answering this question early on can help ensure you maximize your contract benefits. His advice for any negotiation is keep to the following in mind:

• Prepare, prepare, prepare. Employers know when you’re winging it.
•  Gain leverage. The more offers you have, the more leverage.
•  Give yourself adequate time to negotiate.
•  Establish your objectives and anticipate objectives of the employer.
•  Determine the best case, worst case, and most likely scenario before you start negotiating.
•  Try to define nonnegotiable issues.
•  Try to get something each time you give something.
•  Don’t negotiate against yourself.
•  Keep cool and remember that these are people you may have to work with.
•  Be flexible.

View the full presentation (login required), which also covers hot topics in negotiating your contract – more than 1-year base salary, bonuses, student loan repayment.

Visit www.gastro.org/education to see all on-demand education designed specifically for trainees and early career GIs.

Who’s going to negotiate your contract: you or a professional? Lawyer Scott Roman – at a recent AGA Regional Practice Skills Workshop – explained that answering this question early on can help ensure you maximize your contract benefits. His advice for any negotiation is keep to the following in mind:

• Prepare, prepare, prepare. Employers know when you’re winging it.
•  Gain leverage. The more offers you have, the more leverage.
•  Give yourself adequate time to negotiate.
•  Establish your objectives and anticipate objectives of the employer.
•  Determine the best case, worst case, and most likely scenario before you start negotiating.
•  Try to define nonnegotiable issues.
•  Try to get something each time you give something.
•  Don’t negotiate against yourself.
•  Keep cool and remember that these are people you may have to work with.
•  Be flexible.

View the full presentation (login required), which also covers hot topics in negotiating your contract – more than 1-year base salary, bonuses, student loan repayment.

Visit www.gastro.org/education to see all on-demand education designed specifically for trainees and early career GIs.

Who’s going to negotiate your contract: you or a professional? Lawyer Scott Roman – at a recent AGA Regional Practice Skills Workshop – explained that answering this question early on can help ensure you maximize your contract benefits. His advice for any negotiation is keep to the following in mind:

• Prepare, prepare, prepare. Employers know when you’re winging it.
•  Gain leverage. The more offers you have, the more leverage.
•  Give yourself adequate time to negotiate.
•  Establish your objectives and anticipate objectives of the employer.
•  Determine the best case, worst case, and most likely scenario before you start negotiating.
•  Try to define nonnegotiable issues.
•  Try to get something each time you give something.
•  Don’t negotiate against yourself.
•  Keep cool and remember that these are people you may have to work with.
•  Be flexible.

View the full presentation (login required), which also covers hot topics in negotiating your contract – more than 1-year base salary, bonuses, student loan repayment.

Visit www.gastro.org/education to see all on-demand education designed specifically for trainees and early career GIs.

New Orleans – An effective and well-tolerated, evidence-based strategy for managing statin-associated muscle complaints is to rechallenge with the same statin, Douglas S. Paauw, MD, said at the annual meeting of the American College of Physicians.

That being said, it must be recognized that statin-associated muscle symptoms remain an enigma. This was underscored in a recent study by investigators at Hartford (Conn.) Hospital, which suggested a need to reassess the whole concept of statin-associated muscle symptoms, according to Dr. Paauw, professor of medicine at the University of Washington, Seattle.

First things first

Before embarking on same-statin rechallenge, several things should first be done. Step 1 is to check the patient’s thyroid-stimulating hormone, creatine kinase, and serum vitamin D levels. Step 2 is to look for possible explanatory drug interactions, with verapamil and diltiazem being particularly common offenders in statin users.

If a patient with statin-associated muscle symptoms has a low serum vitamin D level, Dr. Paauw will give high-dose supplemental vitamin D. This strategy is supported by a University of Cincinnati prospective study of 146 patients with intolerable muscle symptoms on two or more statins, all of whom had a serum vitamin D below 32 ng/mL. They were placed on long-term vitamin D₂ at 50,000-100,000 units per week and rechallenged with a statin. At 2 years of follow-up while still on supplemental vitamin D, 91% of patients had a normal serum vitamin D, and 95% of these previously statin-intolerant patients were on statin therapy without muscle complaints (N Am J Med Sci. 2015 Mar;7[3]:86-93).

Hypothyroidism increases statin toxicity. “I can’t overstate how important it is to check the thyroid-stimulating hormone to see if we’re dealing with something really simple,” Dr. Paauw said, “because trust me, treating hypothyroidism is much easier than treating statin-associated muscle symptoms.”

It has long been known that fibrates increase the risk of statin toxicity. Much less well recognized is that not all fibrates are the same in this regard: The risk is 15 times greater with gemfibrozil than with fenofibrate. The risk is also higher with verapamil or diltiazem than with nifedipine or amlodipine. Other important causes of drug interactions that increase statin toxicity include amiodarone, azole antifungals, protease inhibitors, erythromycin, and clarithromycin, but not azithromycin.

“Simvastatin and lovastatin are probably the worst as far as drug interactions,” Dr. Paauw cautioned. “They’re cheap, they’ve been generic for a long, long time, and a lot of times insurance companies want to move people to them. I try to move patients away from those two, because they are the dirtiest of the statins as far as side effects and drug interactions.”

When a drug interaction simply cannot be avoided, it’s best to have patients take the drugs 12 hours apart so peak levels don’t overlap, he added.

Same-statin rechallenge

If the checks of TSH, vitamin D, and possible drug interactions don’t turn up anything that needs fixing, it makes sense to launch same-statin rechallenge.

This management strategy was greenlighted by Canadian investigators in a retrospective study of 118 patients who presented to a tertiary lipid clinic with a history of muscle-related symptoms on at least two different statins.

At a median follow-up of 17 months, 71% of rechallenged patients were tolerating the same statin, compared with 53% of those who were switched to a different statin and 57% who were switched to ezetimibe or another nonstatin LDL-lowering drug. Moreover, 50% of patients in the same-statin rechallenge group achieved their target LDL, compared with only 15% switched to nonstatin therapy (Can J Cardiol. 2017 May;33[5]:666-73).

“I like this study; it helps a lot,” Dr. Paauw noted. “I think it’s worthwhile the first time they have muscle pain to get them off the statin and see if they feel better, so you become convinced that the statin may have had something to do with it. Then tell the patient, ‘Let’s just give it another try.’ ”
 

Alternative strategies

In the event of recurrent symptoms after same-statin rechallenge, it’s reasonable to switch to extended-release fluvastatin at 80 mg/day or low-dose rosuvastatin daily. Only if the patient remains symptomatic after trials of a couple of other statins does Dr. Paauw recommend turning to 5 mg of rosuvastatin twice weekly as a last resort.

Twice-weekly rosuvastatin is a popular treatment strategy in patients with intolerable muscle complaints on daily statin therapy. In a study of 40 such patients, twice-weekly rosuvastatin proved to be tolerated by 80% of them (Am J Cardiol. 2008 Jun 15;101[12]:1747-8). But the long-term effectiveness remains unknown.

“I think this is a really good option for our very statin-intolerant patients when nothing else works,” Dr. Paauw explained. “My only concern about this is we have no outcome data. Is twice-weekly rosuvastatin going to help reduce MI risk, especially if we give it for secondary prevention, as well as a daily statin? We know from this study that twice-weekly rosuvastatin can lower the lipids, but we also believe statins do more than just lower lipids. So, daily statin therapy is preferential.”

What about giving coenzyme Q₁₀? It makes sense mechanistically: Coenzyme Q₁₀ is an antioxidant, ubiquinone, and patients with statin-associated muscle symptoms are ubiquinone depleted.

But while oral coenzyme Q₁₀ is a popular OTC treatment for statin-associated muscle complaints, it’s not supported by any good evidence. A meta-analysis of six randomized trials totaling 302 participants found coenzyme Q₁₀ had no impact on symptoms (Mayo Clin Proc. 2015;90[1]:24-34).

In Dr. Paauw’s view, however, those trials didn’t address the proper question.

“The studies that have been done aren’t the right study,“ he said. “The study that needs to be done is for prevention: Do patients who start a statin and coenzyme Q₁₀ at the same time stay on the statin and feel better?”

He reported having no financial conflicts of interest regarding his presentation.

[email protected]

New Orleans – An effective and well-tolerated, evidence-based strategy for managing statin-associated muscle complaints is to rechallenge with the same statin, Douglas S. Paauw, MD, said at the annual meeting of the American College of Physicians.

That being said, it must be recognized that statin-associated muscle symptoms remain an enigma. This was underscored in a recent study by investigators at Hartford (Conn.) Hospital, which suggested a need to reassess the whole concept of statin-associated muscle symptoms, according to Dr. Paauw, professor of medicine at the University of Washington, Seattle.

First things first

Before embarking on same-statin rechallenge, several things should first be done. Step 1 is to check the patient’s thyroid-stimulating hormone, creatine kinase, and serum vitamin D levels. Step 2 is to look for possible explanatory drug interactions, with verapamil and diltiazem being particularly common offenders in statin users.

If a patient with statin-associated muscle symptoms has a low serum vitamin D level, Dr. Paauw will give high-dose supplemental vitamin D. This strategy is supported by a University of Cincinnati prospective study of 146 patients with intolerable muscle symptoms on two or more statins, all of whom had a serum vitamin D below 32 ng/mL. They were placed on long-term vitamin D₂ at 50,000-100,000 units per week and rechallenged with a statin. At 2 years of follow-up while still on supplemental vitamin D, 91% of patients had a normal serum vitamin D, and 95% of these previously statin-intolerant patients were on statin therapy without muscle complaints (N Am J Med Sci. 2015 Mar;7[3]:86-93).

Hypothyroidism increases statin toxicity. “I can’t overstate how important it is to check the thyroid-stimulating hormone to see if we’re dealing with something really simple,” Dr. Paauw said, “because trust me, treating hypothyroidism is much easier than treating statin-associated muscle symptoms.”

It has long been known that fibrates increase the risk of statin toxicity. Much less well recognized is that not all fibrates are the same in this regard: The risk is 15 times greater with gemfibrozil than with fenofibrate. The risk is also higher with verapamil or diltiazem than with nifedipine or amlodipine. Other important causes of drug interactions that increase statin toxicity include amiodarone, azole antifungals, protease inhibitors, erythromycin, and clarithromycin, but not azithromycin.

“Simvastatin and lovastatin are probably the worst as far as drug interactions,” Dr. Paauw cautioned. “They’re cheap, they’ve been generic for a long, long time, and a lot of times insurance companies want to move people to them. I try to move patients away from those two, because they are the dirtiest of the statins as far as side effects and drug interactions.”

When a drug interaction simply cannot be avoided, it’s best to have patients take the drugs 12 hours apart so peak levels don’t overlap, he added.

Same-statin rechallenge

If the checks of TSH, vitamin D, and possible drug interactions don’t turn up anything that needs fixing, it makes sense to launch same-statin rechallenge.

This management strategy was greenlighted by Canadian investigators in a retrospective study of 118 patients who presented to a tertiary lipid clinic with a history of muscle-related symptoms on at least two different statins.

At a median follow-up of 17 months, 71% of rechallenged patients were tolerating the same statin, compared with 53% of those who were switched to a different statin and 57% who were switched to ezetimibe or another nonstatin LDL-lowering drug. Moreover, 50% of patients in the same-statin rechallenge group achieved their target LDL, compared with only 15% switched to nonstatin therapy (Can J Cardiol. 2017 May;33[5]:666-73).

“I like this study; it helps a lot,” Dr. Paauw noted. “I think it’s worthwhile the first time they have muscle pain to get them off the statin and see if they feel better, so you become convinced that the statin may have had something to do with it. Then tell the patient, ‘Let’s just give it another try.’ ”
 

Alternative strategies

In the event of recurrent symptoms after same-statin rechallenge, it’s reasonable to switch to extended-release fluvastatin at 80 mg/day or low-dose rosuvastatin daily. Only if the patient remains symptomatic after trials of a couple of other statins does Dr. Paauw recommend turning to 5 mg of rosuvastatin twice weekly as a last resort.

Twice-weekly rosuvastatin is a popular treatment strategy in patients with intolerable muscle complaints on daily statin therapy. In a study of 40 such patients, twice-weekly rosuvastatin proved to be tolerated by 80% of them (Am J Cardiol. 2008 Jun 15;101[12]:1747-8). But the long-term effectiveness remains unknown.

“I think this is a really good option for our very statin-intolerant patients when nothing else works,” Dr. Paauw explained. “My only concern about this is we have no outcome data. Is twice-weekly rosuvastatin going to help reduce MI risk, especially if we give it for secondary prevention, as well as a daily statin? We know from this study that twice-weekly rosuvastatin can lower the lipids, but we also believe statins do more than just lower lipids. So, daily statin therapy is preferential.”

What about giving coenzyme Q₁₀? It makes sense mechanistically: Coenzyme Q₁₀ is an antioxidant, ubiquinone, and patients with statin-associated muscle symptoms are ubiquinone depleted.

But while oral coenzyme Q₁₀ is a popular OTC treatment for statin-associated muscle complaints, it’s not supported by any good evidence. A meta-analysis of six randomized trials totaling 302 participants found coenzyme Q₁₀ had no impact on symptoms (Mayo Clin Proc. 2015;90[1]:24-34).

In Dr. Paauw’s view, however, those trials didn’t address the proper question.

“The studies that have been done aren’t the right study,“ he said. “The study that needs to be done is for prevention: Do patients who start a statin and coenzyme Q₁₀ at the same time stay on the statin and feel better?”

He reported having no financial conflicts of interest regarding his presentation.

[email protected]

New Orleans – An effective and well-tolerated, evidence-based strategy for managing statin-associated muscle complaints is to rechallenge with the same statin, Douglas S. Paauw, MD, said at the annual meeting of the American College of Physicians.

That being said, it must be recognized that statin-associated muscle symptoms remain an enigma. This was underscored in a recent study by investigators at Hartford (Conn.) Hospital, which suggested a need to reassess the whole concept of statin-associated muscle symptoms, according to Dr. Paauw, professor of medicine at the University of Washington, Seattle.

First things first

Before embarking on same-statin rechallenge, several things should first be done. Step 1 is to check the patient’s thyroid-stimulating hormone, creatine kinase, and serum vitamin D levels. Step 2 is to look for possible explanatory drug interactions, with verapamil and diltiazem being particularly common offenders in statin users.

If a patient with statin-associated muscle symptoms has a low serum vitamin D level, Dr. Paauw will give high-dose supplemental vitamin D. This strategy is supported by a University of Cincinnati prospective study of 146 patients with intolerable muscle symptoms on two or more statins, all of whom had a serum vitamin D below 32 ng/mL. They were placed on long-term vitamin D₂ at 50,000-100,000 units per week and rechallenged with a statin. At 2 years of follow-up while still on supplemental vitamin D, 91% of patients had a normal serum vitamin D, and 95% of these previously statin-intolerant patients were on statin therapy without muscle complaints (N Am J Med Sci. 2015 Mar;7[3]:86-93).

Hypothyroidism increases statin toxicity. “I can’t overstate how important it is to check the thyroid-stimulating hormone to see if we’re dealing with something really simple,” Dr. Paauw said, “because trust me, treating hypothyroidism is much easier than treating statin-associated muscle symptoms.”

It has long been known that fibrates increase the risk of statin toxicity. Much less well recognized is that not all fibrates are the same in this regard: The risk is 15 times greater with gemfibrozil than with fenofibrate. The risk is also higher with verapamil or diltiazem than with nifedipine or amlodipine. Other important causes of drug interactions that increase statin toxicity include amiodarone, azole antifungals, protease inhibitors, erythromycin, and clarithromycin, but not azithromycin.

“Simvastatin and lovastatin are probably the worst as far as drug interactions,” Dr. Paauw cautioned. “They’re cheap, they’ve been generic for a long, long time, and a lot of times insurance companies want to move people to them. I try to move patients away from those two, because they are the dirtiest of the statins as far as side effects and drug interactions.”

When a drug interaction simply cannot be avoided, it’s best to have patients take the drugs 12 hours apart so peak levels don’t overlap, he added.

Same-statin rechallenge

If the checks of TSH, vitamin D, and possible drug interactions don’t turn up anything that needs fixing, it makes sense to launch same-statin rechallenge.

This management strategy was greenlighted by Canadian investigators in a retrospective study of 118 patients who presented to a tertiary lipid clinic with a history of muscle-related symptoms on at least two different statins.

At a median follow-up of 17 months, 71% of rechallenged patients were tolerating the same statin, compared with 53% of those who were switched to a different statin and 57% who were switched to ezetimibe or another nonstatin LDL-lowering drug. Moreover, 50% of patients in the same-statin rechallenge group achieved their target LDL, compared with only 15% switched to nonstatin therapy (Can J Cardiol. 2017 May;33[5]:666-73).

“I like this study; it helps a lot,” Dr. Paauw noted. “I think it’s worthwhile the first time they have muscle pain to get them off the statin and see if they feel better, so you become convinced that the statin may have had something to do with it. Then tell the patient, ‘Let’s just give it another try.’ ”
 

Alternative strategies

In the event of recurrent symptoms after same-statin rechallenge, it’s reasonable to switch to extended-release fluvastatin at 80 mg/day or low-dose rosuvastatin daily. Only if the patient remains symptomatic after trials of a couple of other statins does Dr. Paauw recommend turning to 5 mg of rosuvastatin twice weekly as a last resort.

Twice-weekly rosuvastatin is a popular treatment strategy in patients with intolerable muscle complaints on daily statin therapy. In a study of 40 such patients, twice-weekly rosuvastatin proved to be tolerated by 80% of them (Am J Cardiol. 2008 Jun 15;101[12]:1747-8). But the long-term effectiveness remains unknown.

“I think this is a really good option for our very statin-intolerant patients when nothing else works,” Dr. Paauw explained. “My only concern about this is we have no outcome data. Is twice-weekly rosuvastatin going to help reduce MI risk, especially if we give it for secondary prevention, as well as a daily statin? We know from this study that twice-weekly rosuvastatin can lower the lipids, but we also believe statins do more than just lower lipids. So, daily statin therapy is preferential.”

What about giving coenzyme Q₁₀? It makes sense mechanistically: Coenzyme Q₁₀ is an antioxidant, ubiquinone, and patients with statin-associated muscle symptoms are ubiquinone depleted.

But while oral coenzyme Q₁₀ is a popular OTC treatment for statin-associated muscle complaints, it’s not supported by any good evidence. A meta-analysis of six randomized trials totaling 302 participants found coenzyme Q₁₀ had no impact on symptoms (Mayo Clin Proc. 2015;90[1]:24-34).

In Dr. Paauw’s view, however, those trials didn’t address the proper question.

“The studies that have been done aren’t the right study,“ he said. “The study that needs to be done is for prevention: Do patients who start a statin and coenzyme Q₁₀ at the same time stay on the statin and feel better?”

He reported having no financial conflicts of interest regarding his presentation.

[email protected]

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.

Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.

When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.

At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.

The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.

Dr. Candler's interview:

Dr. DeSalvo's interview:

Dr. Ende's interview:

[email protected]

SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.

NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.

Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.

When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.

At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.

The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.

Dr. Candler's interview:

Dr. DeSalvo's interview:

Dr. Ende's interview:

[email protected]

SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.

NEW ORLEANS – What happens outside the exam room often plays a crucial, and crucially overlooked, role in how well or poorly patients respond to medical therapy.

Social determinants – from the bus ride to a clinic to fitting medication compliance into a three-job work day – are at the center of a new push by the American College of Physicians to improve patient care and awaken physicians to the nonmedical factors that frustrate treatment and fuel outcomes failures.

When it comes to patients’ health, American College of Physicians President Jack Ende, MD, says it’s often ZIP code, not gene code, that can make all the difference.

At the annual meeting of the American College of Physicians, Dr. Ende of the University of Pennsylvania, Philadelphia; Sarah Candler, MD, of Baylor College of Medicine, Houston; and Karen DeSalvo, MD, of the University of Texas, Austin, outlined how physicians can look beyond biology and into patients’ social environments, and they shared resources physicians can use to counter social determinants that harm health.

The ACP published a position paper on social determinants of health in the Annals of Internal Medicine.

Dr. Candler's interview:

Dr. DeSalvo's interview:

Dr. Ende's interview:

[email protected]

SOURCE: Ann Intern Med. 2018 Apr 17;168(8):577-8.

A call to push pause on a Medicare payment program, it’s been a busy week at the FDA, ambulatory blood pressure measures outperform the office, and are fast food swamps to blame for more type 1 diabetes?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

A call to push pause on a Medicare payment program, it’s been a busy week at the FDA, ambulatory blood pressure measures outperform the office, and are fast food swamps to blame for more type 1 diabetes?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

A call to push pause on a Medicare payment program, it’s been a busy week at the FDA, ambulatory blood pressure measures outperform the office, and are fast food swamps to blame for more type 1 diabetes?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

Research Hospital/Seth Dixon

Germline variants in IKZF1 can predispose carriers to acute lymphoblastic leukemia (ALL), according to a study published in Cancer Cell.

The research began with the discovery of an IKZF1 variant in 3 generations of a German family affected by pediatric ALL.

Researchers then analyzed data from nearly 5000 children with ALL and identified 27 additional germline variants in IKZF1.

These variants were present in 0.9% of the patients analyzed, and most of the patients with the variants had B-cell ALL.

“This finding adds to the growing body of evidence that, while germline variations still account for a small percentage of pediatric ALL cases overall, more children than previously recognized inherit a predisposition to develop ALL,” said Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

In the Cancer Cell paper, Dr Mullighan and his colleagues report the discovery of a germline deletion variant in IKZF1 (c.del556 or D186fs), which was present in 3 generations of a family.

Two of the 6 family members with this variant had developed B-ALL as children and died. The remaining 4 subjects are apparently healthy, despite having reduced numbers of B cells.

To build upon this discovery, the researchers performed targeted sequencing of IKZF1 in 4963 children with ALL.

This revealed 27 additional IKZF1 variants in 43 patients, most of whom had B-ALL. (One patient had T-cell ALL, and, for 8 patients, their subtype was unknown.)

The researchers noted that the variants were distributed across the gene.

“The pattern of IKZF1 variants was surprising because many of the variants were in regions of the gene that are rarely mutated in leukemic cells,” said study author Jun J. Yang, PhD, of St. Jude. “These regions of the gene have not been well characterized.”

The researchers also found that 22 of the 28 IKZF1 variants adversely affect gene function, while the remaining 6 variants appear to be benign.

The team said the deleterious variants impair DNA binding and regulation of transcriptional targets, induce aberrant leukemic cell adhesion, and reduce ALL cells’ sensitivity to treatment with dasatinib and dexamethasone.

The researchers identified the most deleterious variants as 5 that are located outside of the zinc-finger domains (M31V, M347V, R423C, A434G, and L449F), 2 variants affecting the N-terminal DNA-binding domain (R162P and H163Y), 2 truncating nonsense variants (M306* and C394*), and the frameshift variant discovered in the German family (D186fs).

“This [research] will expand the number of genes to consider when screening for predisposition to leukemia, particularly B-ALL,” said study author Kim Nichols, of St. Jude.

“And while not everyone carrying a germline IKZF1 variant will develop leukemia, these results will help us educate families about the potential risk of leukemia.”

Research Hospital/Seth Dixon

Germline variants in IKZF1 can predispose carriers to acute lymphoblastic leukemia (ALL), according to a study published in Cancer Cell.

The research began with the discovery of an IKZF1 variant in 3 generations of a German family affected by pediatric ALL.

Researchers then analyzed data from nearly 5000 children with ALL and identified 27 additional germline variants in IKZF1.

These variants were present in 0.9% of the patients analyzed, and most of the patients with the variants had B-cell ALL.

“This finding adds to the growing body of evidence that, while germline variations still account for a small percentage of pediatric ALL cases overall, more children than previously recognized inherit a predisposition to develop ALL,” said Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

In the Cancer Cell paper, Dr Mullighan and his colleagues report the discovery of a germline deletion variant in IKZF1 (c.del556 or D186fs), which was present in 3 generations of a family.

Two of the 6 family members with this variant had developed B-ALL as children and died. The remaining 4 subjects are apparently healthy, despite having reduced numbers of B cells.

To build upon this discovery, the researchers performed targeted sequencing of IKZF1 in 4963 children with ALL.

This revealed 27 additional IKZF1 variants in 43 patients, most of whom had B-ALL. (One patient had T-cell ALL, and, for 8 patients, their subtype was unknown.)

The researchers noted that the variants were distributed across the gene.

“The pattern of IKZF1 variants was surprising because many of the variants were in regions of the gene that are rarely mutated in leukemic cells,” said study author Jun J. Yang, PhD, of St. Jude. “These regions of the gene have not been well characterized.”

The researchers also found that 22 of the 28 IKZF1 variants adversely affect gene function, while the remaining 6 variants appear to be benign.

The team said the deleterious variants impair DNA binding and regulation of transcriptional targets, induce aberrant leukemic cell adhesion, and reduce ALL cells’ sensitivity to treatment with dasatinib and dexamethasone.

The researchers identified the most deleterious variants as 5 that are located outside of the zinc-finger domains (M31V, M347V, R423C, A434G, and L449F), 2 variants affecting the N-terminal DNA-binding domain (R162P and H163Y), 2 truncating nonsense variants (M306* and C394*), and the frameshift variant discovered in the German family (D186fs).

“This [research] will expand the number of genes to consider when screening for predisposition to leukemia, particularly B-ALL,” said study author Kim Nichols, of St. Jude.

“And while not everyone carrying a germline IKZF1 variant will develop leukemia, these results will help us educate families about the potential risk of leukemia.”

Research Hospital/Seth Dixon

Germline variants in IKZF1 can predispose carriers to acute lymphoblastic leukemia (ALL), according to a study published in Cancer Cell.

The research began with the discovery of an IKZF1 variant in 3 generations of a German family affected by pediatric ALL.

Researchers then analyzed data from nearly 5000 children with ALL and identified 27 additional germline variants in IKZF1.

These variants were present in 0.9% of the patients analyzed, and most of the patients with the variants had B-cell ALL.

“This finding adds to the growing body of evidence that, while germline variations still account for a small percentage of pediatric ALL cases overall, more children than previously recognized inherit a predisposition to develop ALL,” said Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

In the Cancer Cell paper, Dr Mullighan and his colleagues report the discovery of a germline deletion variant in IKZF1 (c.del556 or D186fs), which was present in 3 generations of a family.

Two of the 6 family members with this variant had developed B-ALL as children and died. The remaining 4 subjects are apparently healthy, despite having reduced numbers of B cells.

To build upon this discovery, the researchers performed targeted sequencing of IKZF1 in 4963 children with ALL.

This revealed 27 additional IKZF1 variants in 43 patients, most of whom had B-ALL. (One patient had T-cell ALL, and, for 8 patients, their subtype was unknown.)

The researchers noted that the variants were distributed across the gene.

“The pattern of IKZF1 variants was surprising because many of the variants were in regions of the gene that are rarely mutated in leukemic cells,” said study author Jun J. Yang, PhD, of St. Jude. “These regions of the gene have not been well characterized.”

The researchers also found that 22 of the 28 IKZF1 variants adversely affect gene function, while the remaining 6 variants appear to be benign.

The team said the deleterious variants impair DNA binding and regulation of transcriptional targets, induce aberrant leukemic cell adhesion, and reduce ALL cells’ sensitivity to treatment with dasatinib and dexamethasone.

The researchers identified the most deleterious variants as 5 that are located outside of the zinc-finger domains (M31V, M347V, R423C, A434G, and L449F), 2 variants affecting the N-terminal DNA-binding domain (R162P and H163Y), 2 truncating nonsense variants (M306* and C394*), and the frameshift variant discovered in the German family (D186fs).

“This [research] will expand the number of genes to consider when screening for predisposition to leukemia, particularly B-ALL,” said study author Kim Nichols, of St. Jude.

“And while not everyone carrying a germline IKZF1 variant will develop leukemia, these results will help us educate families about the potential risk of leukemia.”

Photo by Rhoda Baer

CHICAGO—Preclinical research suggests the pan-FLT3/pan-BTK inhibitor CG’806 is more effective than other kinase inhibitors in fighting certain hematologic malignancies.

In one study, CG’806 proved more potent than comparator drugs in primary samples of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).

In another study, CG’806 demonstrated greater cytotoxicity than comparators in a range of malignant B cell lines.

Data from both studies were presented at the AACR Annual Meeting 2018 (abstracts 791 and 794).

The research was supported by Aptose Biosciences, Inc., the company developing CG’806.

CG’806 is a small molecule that inhibits wild-type (WT) FLT3, as well as FLT3 housing the ITD mutation or with point mutations in the tyrosine kinase domain (TKD, including D835G, D835Y, D835H) or in the gatekeeper region (F691L). CG’806 also inhibits BTK-WT and BTK-C481S.

Abstract 791

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented results with CG’806 in primary patient samples.

The team found that CG’806 demonstrated greater potency against AML samples relative to other FLT3 inhibitors.

Median IC₅₀ values in 188 AML patient samples were 0.0765 µM for CG’806, 0.125 µM for gilteritinib, 0.199 µM for quizartinib, 0.551 µM for dovitinib, 2.25 µM for midostaurin, 2.93 µM for sorafenib, and 5.01 µM for crenolanib.

The researchers said CG’806 sensitivity was enhanced in FLT3-ITD and FLT3-TKD positive cases.

In CLL patient samples, CG’806 exhibited greater potency and a greater range of activity than the BTK inhibitor ibrutinib. Across 95 CLL samples, the median IC₅₀ values were 0.114 µM for CG’806 and 4.09 µM for ibrutinib.

The researchers said this greater potency of CG’806 may be due to the activity of CG’806 on CSF1R, which has been identified as a therapeutic target in CLL.

“The clinical benefit of current FLT3 inhibitors in AML is transient, as resistance develops after several months of treatment,” Dr Kurtz noted. “Similarly, ibrutinib . . . is limited by acquired resistance as well as refractory disease and tolerance challenges. As a pan-FLT3/pan-BTK inhibitor . . ., CG’806 offers important potential to address these limitations.”

Abstract 794

Hongying Zhang, MD, PhD, of Aptose Biosciences, and her colleagues presented results with CG’806 in malignant B-cell and AML cell lines.

The researchers found that CG’806 inhibited FLT3-ITD signaling and induced apoptosis more effectively than quizartinib in FLT3-ITD AML cells (MV4-11). The team noted that CG’806 caused G0/G1 cell-cycle arrest in the cells.

CG’806 also exhibited greater cytotoxic activity than quizartinib in FLT3-WT AML cell lines (KG-1 and NOMO-1).

In addition, CG’806 was more potent than quizartinib, gilteritinib, and crenolanib in Ba/F3 cells transfected with FLT3-WT, ITD, D835Y, and ITD-F691. CG’806 was more potent than quizartinib and crenolanib—but not gilteritinib—in Ba/F3 cells transfected with FLT3-ITD-D835Y.

The researchers said they found that CG’806 inhibits BTK, AURK, and downstream signals in FLT3-WT AML cells.

The team also found that CG’806 decreased BTK phosphorylation in all tested cell lines of B-cell malignancies. This included acute lymphoblastic leukemia, mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma cell lines.

Across all cell lines, CG’806 killed malignant B cells more effectively than ibrutinib. And CG’806 was “equally potent” against WT and C481S-mutant BTK, according to the researchers.

The team also said CG’806 inhibited AURK and induced polyploidy in B-cell malignancies.

“[C]G’806 has demonstrated the ability to kill a broad range of AML and B-cell malignancies through inhibition of multiple oncogenic pathways,” said William G. Rice, PhD, chairman and chief executive officer of Aptose.

“These studies are critical for understanding how to develop and position CG’806 as we prepare for clinical development in these challenging hematologic malignancies.”

Photo by Rhoda Baer

CHICAGO—Preclinical research suggests the pan-FLT3/pan-BTK inhibitor CG’806 is more effective than other kinase inhibitors in fighting certain hematologic malignancies.

In one study, CG’806 proved more potent than comparator drugs in primary samples of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).

In another study, CG’806 demonstrated greater cytotoxicity than comparators in a range of malignant B cell lines.

Data from both studies were presented at the AACR Annual Meeting 2018 (abstracts 791 and 794).

The research was supported by Aptose Biosciences, Inc., the company developing CG’806.

CG’806 is a small molecule that inhibits wild-type (WT) FLT3, as well as FLT3 housing the ITD mutation or with point mutations in the tyrosine kinase domain (TKD, including D835G, D835Y, D835H) or in the gatekeeper region (F691L). CG’806 also inhibits BTK-WT and BTK-C481S.

Abstract 791

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented results with CG’806 in primary patient samples.

The team found that CG’806 demonstrated greater potency against AML samples relative to other FLT3 inhibitors.

Median IC₅₀ values in 188 AML patient samples were 0.0765 µM for CG’806, 0.125 µM for gilteritinib, 0.199 µM for quizartinib, 0.551 µM for dovitinib, 2.25 µM for midostaurin, 2.93 µM for sorafenib, and 5.01 µM for crenolanib.

The researchers said CG’806 sensitivity was enhanced in FLT3-ITD and FLT3-TKD positive cases.

In CLL patient samples, CG’806 exhibited greater potency and a greater range of activity than the BTK inhibitor ibrutinib. Across 95 CLL samples, the median IC₅₀ values were 0.114 µM for CG’806 and 4.09 µM for ibrutinib.

The researchers said this greater potency of CG’806 may be due to the activity of CG’806 on CSF1R, which has been identified as a therapeutic target in CLL.

“The clinical benefit of current FLT3 inhibitors in AML is transient, as resistance develops after several months of treatment,” Dr Kurtz noted. “Similarly, ibrutinib . . . is limited by acquired resistance as well as refractory disease and tolerance challenges. As a pan-FLT3/pan-BTK inhibitor . . ., CG’806 offers important potential to address these limitations.”

Abstract 794

Hongying Zhang, MD, PhD, of Aptose Biosciences, and her colleagues presented results with CG’806 in malignant B-cell and AML cell lines.

The researchers found that CG’806 inhibited FLT3-ITD signaling and induced apoptosis more effectively than quizartinib in FLT3-ITD AML cells (MV4-11). The team noted that CG’806 caused G0/G1 cell-cycle arrest in the cells.

CG’806 also exhibited greater cytotoxic activity than quizartinib in FLT3-WT AML cell lines (KG-1 and NOMO-1).

In addition, CG’806 was more potent than quizartinib, gilteritinib, and crenolanib in Ba/F3 cells transfected with FLT3-WT, ITD, D835Y, and ITD-F691. CG’806 was more potent than quizartinib and crenolanib—but not gilteritinib—in Ba/F3 cells transfected with FLT3-ITD-D835Y.

The researchers said they found that CG’806 inhibits BTK, AURK, and downstream signals in FLT3-WT AML cells.

The team also found that CG’806 decreased BTK phosphorylation in all tested cell lines of B-cell malignancies. This included acute lymphoblastic leukemia, mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma cell lines.

Across all cell lines, CG’806 killed malignant B cells more effectively than ibrutinib. And CG’806 was “equally potent” against WT and C481S-mutant BTK, according to the researchers.

The team also said CG’806 inhibited AURK and induced polyploidy in B-cell malignancies.

“[C]G’806 has demonstrated the ability to kill a broad range of AML and B-cell malignancies through inhibition of multiple oncogenic pathways,” said William G. Rice, PhD, chairman and chief executive officer of Aptose.

“These studies are critical for understanding how to develop and position CG’806 as we prepare for clinical development in these challenging hematologic malignancies.”

Photo by Rhoda Baer

CHICAGO—Preclinical research suggests the pan-FLT3/pan-BTK inhibitor CG’806 is more effective than other kinase inhibitors in fighting certain hematologic malignancies.

In one study, CG’806 proved more potent than comparator drugs in primary samples of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).

In another study, CG’806 demonstrated greater cytotoxicity than comparators in a range of malignant B cell lines.

Data from both studies were presented at the AACR Annual Meeting 2018 (abstracts 791 and 794).

The research was supported by Aptose Biosciences, Inc., the company developing CG’806.

CG’806 is a small molecule that inhibits wild-type (WT) FLT3, as well as FLT3 housing the ITD mutation or with point mutations in the tyrosine kinase domain (TKD, including D835G, D835Y, D835H) or in the gatekeeper region (F691L). CG’806 also inhibits BTK-WT and BTK-C481S.

Abstract 791

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented results with CG’806 in primary patient samples.

The team found that CG’806 demonstrated greater potency against AML samples relative to other FLT3 inhibitors.

Median IC₅₀ values in 188 AML patient samples were 0.0765 µM for CG’806, 0.125 µM for gilteritinib, 0.199 µM for quizartinib, 0.551 µM for dovitinib, 2.25 µM for midostaurin, 2.93 µM for sorafenib, and 5.01 µM for crenolanib.

The researchers said CG’806 sensitivity was enhanced in FLT3-ITD and FLT3-TKD positive cases.

In CLL patient samples, CG’806 exhibited greater potency and a greater range of activity than the BTK inhibitor ibrutinib. Across 95 CLL samples, the median IC₅₀ values were 0.114 µM for CG’806 and 4.09 µM for ibrutinib.

The researchers said this greater potency of CG’806 may be due to the activity of CG’806 on CSF1R, which has been identified as a therapeutic target in CLL.

“The clinical benefit of current FLT3 inhibitors in AML is transient, as resistance develops after several months of treatment,” Dr Kurtz noted. “Similarly, ibrutinib . . . is limited by acquired resistance as well as refractory disease and tolerance challenges. As a pan-FLT3/pan-BTK inhibitor . . ., CG’806 offers important potential to address these limitations.”

Abstract 794

Hongying Zhang, MD, PhD, of Aptose Biosciences, and her colleagues presented results with CG’806 in malignant B-cell and AML cell lines.

The researchers found that CG’806 inhibited FLT3-ITD signaling and induced apoptosis more effectively than quizartinib in FLT3-ITD AML cells (MV4-11). The team noted that CG’806 caused G0/G1 cell-cycle arrest in the cells.

CG’806 also exhibited greater cytotoxic activity than quizartinib in FLT3-WT AML cell lines (KG-1 and NOMO-1).

In addition, CG’806 was more potent than quizartinib, gilteritinib, and crenolanib in Ba/F3 cells transfected with FLT3-WT, ITD, D835Y, and ITD-F691. CG’806 was more potent than quizartinib and crenolanib—but not gilteritinib—in Ba/F3 cells transfected with FLT3-ITD-D835Y.

The researchers said they found that CG’806 inhibits BTK, AURK, and downstream signals in FLT3-WT AML cells.

The team also found that CG’806 decreased BTK phosphorylation in all tested cell lines of B-cell malignancies. This included acute lymphoblastic leukemia, mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma cell lines.

Across all cell lines, CG’806 killed malignant B cells more effectively than ibrutinib. And CG’806 was “equally potent” against WT and C481S-mutant BTK, according to the researchers.

The team also said CG’806 inhibited AURK and induced polyploidy in B-cell malignancies.

“[C]G’806 has demonstrated the ability to kill a broad range of AML and B-cell malignancies through inhibition of multiple oncogenic pathways,” said William G. Rice, PhD, chairman and chief executive officer of Aptose.

“These studies are critical for understanding how to develop and position CG’806 as we prepare for clinical development in these challenging hematologic malignancies.”