LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com

SAN DIEGO – A chimeric antigen receptor (CAR) targeting both CD19 and CD22 shows promising safety and efficacy for the treatment of relapsed or refractory B-cell malignancies in adults, according to early findings from a phase 1 trial of the novel bispecific CAR.

Of six patients with diffuse large B-cell lymphoma (DLBCL) and two patients with B-cell acute lymphoblastic leukemia (B-ALL) enrolled in the single-institution dose escalation study and available for safety analysis after the bispecific CAR T-cell infusion, five developed reversible grade 1 cytokine release syndrome (CRS) and one developed grade 2 CRS requiring treatment with tocilizumab, Nasheed Hossain, MD, reported at the annual meeting of the American Society of Hematology.

Additionally, two patients developed grade 1 neurotoxicity, and one developed grade 2 neurotoxicity requiring treatment with dexamethasone.

“But no dose-limiting toxicities have been encountered thus far,” said Dr. Hossain of Loyola University Medical Center, Chicago. “With regard to efficacy, the DLBCL overall response rate is 60%, with 1 [complete response] and 2 [partial responses] at day 28 and day 90, and the ALL overall response rate is 100%, with 1 CR and 1 PR at day 28.

“With longer follow-up, five patients have relapsed and biopsies at the time of progression all showed ongoing CD19 expression,” he said, adding that all enrolled patients are alive, except for one patient who died from disease progression.


Study participants were adults aged 35-75 years with DLBCL or B-ALL that was refractory to standard therapies.

“Our primary objectives are twofold: One is to determine the feasibility of making our CAR ... and [the other] is to assess the safety using an escalating CAR dose following standard cyclophosphamide/fludarabine conditioning,” Dr. Hossain said.

The dose assessed in the current analysis was 1 x 10⁶ CAR T cells/kg; other planned doses include 3 x 10⁶ CAR T cells/kg and 1 x 10⁷ CAR T cells/kg, he said.

All patients underwent lymphodepletion with cyclophosphamide (500 mg/m² daily x 3 doses) and fludarabine (30 mg/m² daily x 3 doses) followed by CAR T-cell infusion 2 days later.

The findings of this ongoing study – the first in-human study of a bispecific loop CAR in the United States – suggest that the novel CAR has low toxicity and promising efficacy, Dr. Hossain said.

Currently approved therapies target CD19 alone, he said, noting that they all use the same anti-CD19 domain, but different costimulatory domains, and have good clinical efficacy of greater than 70% CRs in ALL and up to 52% CRs in DLBCL.

“But questions remain about determining the durability of response and the causes of therapy failure,” he said.

One common cause of treatment failure is CD19 antigen loss, and efforts to reduce such antigen loss using bispecific loop CARs targeting both CD19 and CD22 have shown promise. The CAR construct evaluated in this study was developed to target CD19 and CD22 with intracellular signaling domains incorporating 4-1BB and CD3-zeta to overcome CD19 immune escape.

“We have now escalated the dose to 3 x 10⁶ CAR T cells/kg ... and an expansion study of 60 patients will follow,” Dr. Hossain said.

A companion phase 1 pediatric trial using the same CAR construct is also underway, with preliminary data presented at the ASH meeting demonstrating safety and tolerability in children with relapsed or refractory B-cell ALL.

Dr. Hossain reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Hossain N et al. ASH 2018, Abstract 490.

SAN DIEGO – A chimeric antigen receptor (CAR) targeting both CD19 and CD22 shows promising safety and efficacy for the treatment of relapsed or refractory B-cell malignancies in adults, according to early findings from a phase 1 trial of the novel bispecific CAR.

Of six patients with diffuse large B-cell lymphoma (DLBCL) and two patients with B-cell acute lymphoblastic leukemia (B-ALL) enrolled in the single-institution dose escalation study and available for safety analysis after the bispecific CAR T-cell infusion, five developed reversible grade 1 cytokine release syndrome (CRS) and one developed grade 2 CRS requiring treatment with tocilizumab, Nasheed Hossain, MD, reported at the annual meeting of the American Society of Hematology.

Additionally, two patients developed grade 1 neurotoxicity, and one developed grade 2 neurotoxicity requiring treatment with dexamethasone.

“But no dose-limiting toxicities have been encountered thus far,” said Dr. Hossain of Loyola University Medical Center, Chicago. “With regard to efficacy, the DLBCL overall response rate is 60%, with 1 [complete response] and 2 [partial responses] at day 28 and day 90, and the ALL overall response rate is 100%, with 1 CR and 1 PR at day 28.

“With longer follow-up, five patients have relapsed and biopsies at the time of progression all showed ongoing CD19 expression,” he said, adding that all enrolled patients are alive, except for one patient who died from disease progression.


Study participants were adults aged 35-75 years with DLBCL or B-ALL that was refractory to standard therapies.

“Our primary objectives are twofold: One is to determine the feasibility of making our CAR ... and [the other] is to assess the safety using an escalating CAR dose following standard cyclophosphamide/fludarabine conditioning,” Dr. Hossain said.

The dose assessed in the current analysis was 1 x 10⁶ CAR T cells/kg; other planned doses include 3 x 10⁶ CAR T cells/kg and 1 x 10⁷ CAR T cells/kg, he said.

All patients underwent lymphodepletion with cyclophosphamide (500 mg/m² daily x 3 doses) and fludarabine (30 mg/m² daily x 3 doses) followed by CAR T-cell infusion 2 days later.

The findings of this ongoing study – the first in-human study of a bispecific loop CAR in the United States – suggest that the novel CAR has low toxicity and promising efficacy, Dr. Hossain said.

Currently approved therapies target CD19 alone, he said, noting that they all use the same anti-CD19 domain, but different costimulatory domains, and have good clinical efficacy of greater than 70% CRs in ALL and up to 52% CRs in DLBCL.

“But questions remain about determining the durability of response and the causes of therapy failure,” he said.

One common cause of treatment failure is CD19 antigen loss, and efforts to reduce such antigen loss using bispecific loop CARs targeting both CD19 and CD22 have shown promise. The CAR construct evaluated in this study was developed to target CD19 and CD22 with intracellular signaling domains incorporating 4-1BB and CD3-zeta to overcome CD19 immune escape.

“We have now escalated the dose to 3 x 10⁶ CAR T cells/kg ... and an expansion study of 60 patients will follow,” Dr. Hossain said.

A companion phase 1 pediatric trial using the same CAR construct is also underway, with preliminary data presented at the ASH meeting demonstrating safety and tolerability in children with relapsed or refractory B-cell ALL.

Dr. Hossain reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Hossain N et al. ASH 2018, Abstract 490.

SAN DIEGO – A chimeric antigen receptor (CAR) targeting both CD19 and CD22 shows promising safety and efficacy for the treatment of relapsed or refractory B-cell malignancies in adults, according to early findings from a phase 1 trial of the novel bispecific CAR.

Of six patients with diffuse large B-cell lymphoma (DLBCL) and two patients with B-cell acute lymphoblastic leukemia (B-ALL) enrolled in the single-institution dose escalation study and available for safety analysis after the bispecific CAR T-cell infusion, five developed reversible grade 1 cytokine release syndrome (CRS) and one developed grade 2 CRS requiring treatment with tocilizumab, Nasheed Hossain, MD, reported at the annual meeting of the American Society of Hematology.

Additionally, two patients developed grade 1 neurotoxicity, and one developed grade 2 neurotoxicity requiring treatment with dexamethasone.

“But no dose-limiting toxicities have been encountered thus far,” said Dr. Hossain of Loyola University Medical Center, Chicago. “With regard to efficacy, the DLBCL overall response rate is 60%, with 1 [complete response] and 2 [partial responses] at day 28 and day 90, and the ALL overall response rate is 100%, with 1 CR and 1 PR at day 28.

“With longer follow-up, five patients have relapsed and biopsies at the time of progression all showed ongoing CD19 expression,” he said, adding that all enrolled patients are alive, except for one patient who died from disease progression.


Study participants were adults aged 35-75 years with DLBCL or B-ALL that was refractory to standard therapies.

“Our primary objectives are twofold: One is to determine the feasibility of making our CAR ... and [the other] is to assess the safety using an escalating CAR dose following standard cyclophosphamide/fludarabine conditioning,” Dr. Hossain said.

The dose assessed in the current analysis was 1 x 10⁶ CAR T cells/kg; other planned doses include 3 x 10⁶ CAR T cells/kg and 1 x 10⁷ CAR T cells/kg, he said.

All patients underwent lymphodepletion with cyclophosphamide (500 mg/m² daily x 3 doses) and fludarabine (30 mg/m² daily x 3 doses) followed by CAR T-cell infusion 2 days later.

The findings of this ongoing study – the first in-human study of a bispecific loop CAR in the United States – suggest that the novel CAR has low toxicity and promising efficacy, Dr. Hossain said.

Currently approved therapies target CD19 alone, he said, noting that they all use the same anti-CD19 domain, but different costimulatory domains, and have good clinical efficacy of greater than 70% CRs in ALL and up to 52% CRs in DLBCL.

“But questions remain about determining the durability of response and the causes of therapy failure,” he said.

One common cause of treatment failure is CD19 antigen loss, and efforts to reduce such antigen loss using bispecific loop CARs targeting both CD19 and CD22 have shown promise. The CAR construct evaluated in this study was developed to target CD19 and CD22 with intracellular signaling domains incorporating 4-1BB and CD3-zeta to overcome CD19 immune escape.

“We have now escalated the dose to 3 x 10⁶ CAR T cells/kg ... and an expansion study of 60 patients will follow,” Dr. Hossain said.

A companion phase 1 pediatric trial using the same CAR construct is also underway, with preliminary data presented at the ASH meeting demonstrating safety and tolerability in children with relapsed or refractory B-cell ALL.

Dr. Hossain reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Hossain N et al. ASH 2018, Abstract 490.

Fertility preservation, imaging and radiotherapy guidelines, and best practices in relapse or salvage therapy for primary mediastinal B-cell lymphoma (PMBCL) are all highlighted in a new good practice paper from the British Society for Haematology.

Though PMBCL was previously thought of as a subtype of diffuse large B-cell lymphoma, “gene expression profiling data has shown it to be a separate clinicopathological entity with evidence of an overlap with classic Hodgkin lymphoma,” said Kate Cwynarski, MD, PhD, of University College London Hospitals NHS Foundation Trust in England, and her coauthors. The recommendations were published in the British Journal of Haematology.

PMBCL makes up 2%-4% of non-Hodgkin lymphomas, they said; a bulky anterior mediastinal mass is the usual initial presentation. PMBCL does not usually spread beyond the thoracic cavity.

Biopsy, which should be reviewed by a hematopathologist, is required for a histological diagnosis of PMBCL. A multidisciplinary team should review the clinical presentation, pathology, and management plan, according to the good practice paper authors. This was a strong recommendation backed by a high level of evidence.

In addition, patients should receive positron emission tomography–computed tomography (PET/CT) at diagnosis, before steroids are administered, if possible, as standard of care. Results from the PET/CT should be reported in accordance with international guidelines. These strong recommendations are backed by high-quality evidence.

If PET/CT is performed, then “a bone marrow biopsy is not considered essential,” said Dr. Cwynarski and her coauthors. However, if the findings would influence management, such as when there is extranodal disease that presents central nervous system opportunities, then bone marrow biopsy should be performed. It should also be performed when cytotoxic therapy was initiated before PET/CT could be done. This is a weak recommendation supported by moderate evidence.

Since patients with PMBCL are usually young adults at presentation, it’s important to consider fertility preservation in the face of chemotherapy. For males, semen preservation should be offered. Female patients may not be able to postpone treatment long enough to accomplish egg harvesting. The risk of infertility and premature ovarian failure will depend on the treatment regimen, so “the risks of each individual therapeutic regimen should be discussed with the patient,” Dr. Cwynarski and her colleagues said.

If a patient is diagnosed with PMBCL while pregnant, treatment should be managed in conjunction with high-risk obstetrics and anesthesia specialists. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used in pregnancy, and immunotherapy without antimetabolites can be considered in the second and third trimesters, according to the good practice paper. These are strong fertility and pregnancy recommendations, backed by moderate to low-quality evidence.

If superior vena cava obstruction causes thrombosis, local standard of care for anticoagulation should be used, but therapy-induced thrombocytopenia should be taken into consideration.

There is a lack of prospective, randomized studies to guide treatment decisions in PMBCL, according to the paper. Still, adding rituximab improves both response rates and duration of remission, they noted.

The standard of care for treatment is six cycles of R-CHOP and involved site radiotherapy (ISRT). If the patient is being cared for at a site that can manage the complexities of dose adjustment and monitoring, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) without ISRT is an alternative, according to the good practice paper.

All patients should be offered clinical trial participation when feasible, a strong recommendation based on high-quality evidence.

To assess the response to therapy, R-CHOP and ISRT recipients not participating in a clinical trial should receive a PET-CT scan 2-3 months after treatment is completed, and DA-EPOCH-R patients should receive their scan 6 weeks after the end of therapy. For all patients, Deauville criteria should be used in reporting response scan results. These strong recommendations about posttherapy imaging are based on moderate-quality evidence.

The rate of relapse and refractory disease is relatively low at about 10%-30%, Dr. Cwynarski and her colleagues said. Relapse usually happens within the first year and is rare after 2 years; extranodal disease is common, but usually spares the central nervous system and bone marrow. The good practice paper authors strongly recommend, based on high-quality evidence, that biopsy and fluorodeoxyglucose-PET/CT should be performed with relapse.

Radiotherapy can be considered if the relapse is localized and the patient didn’t receive initial radiotherapy, a strong recommendation with moderate evidence to support it.

Salvage regimens for patients who have not previously achieved complete metabolic response lack a disease-specific evidence base, noted Dr. Cwynarski and her colleagues. Taking this into consideration, a PMBCL salvage regimen should be the same as that offered to patients with relapsed diffused large B-cell lymphoma. High-dose therapy and autologous stem cell transplantation is appropriate for responsive disease.

If radiotherapy had not been given previously, it should be considered either pre- or post transplant. This, along with the other salvage therapy guidance, is a weak recommendation, backed by moderate evidence.

For longer-term follow-up, asymptomatic patients should not have routine imaging, a strong recommendation with moderate evidence. “[P]atients who remain in remission may be considered for discharge back to primary care,” Dr. Cwynarski and her coauthors said, making a weak recommendation based on low-quality evidence. Patients and their primary care providers should know about the potential for such long-term complications as cardiac toxicities and second malignancies.

koakes@mdedge.com

SOURCE: Cwynarski K et al. Br J Haematol. 2019 Jan 4. doi:10.1111/bjh.15731

Fertility preservation, imaging and radiotherapy guidelines, and best practices in relapse or salvage therapy for primary mediastinal B-cell lymphoma (PMBCL) are all highlighted in a new good practice paper from the British Society for Haematology.

Though PMBCL was previously thought of as a subtype of diffuse large B-cell lymphoma, “gene expression profiling data has shown it to be a separate clinicopathological entity with evidence of an overlap with classic Hodgkin lymphoma,” said Kate Cwynarski, MD, PhD, of University College London Hospitals NHS Foundation Trust in England, and her coauthors. The recommendations were published in the British Journal of Haematology.

PMBCL makes up 2%-4% of non-Hodgkin lymphomas, they said; a bulky anterior mediastinal mass is the usual initial presentation. PMBCL does not usually spread beyond the thoracic cavity.

Biopsy, which should be reviewed by a hematopathologist, is required for a histological diagnosis of PMBCL. A multidisciplinary team should review the clinical presentation, pathology, and management plan, according to the good practice paper authors. This was a strong recommendation backed by a high level of evidence.

In addition, patients should receive positron emission tomography–computed tomography (PET/CT) at diagnosis, before steroids are administered, if possible, as standard of care. Results from the PET/CT should be reported in accordance with international guidelines. These strong recommendations are backed by high-quality evidence.

If PET/CT is performed, then “a bone marrow biopsy is not considered essential,” said Dr. Cwynarski and her coauthors. However, if the findings would influence management, such as when there is extranodal disease that presents central nervous system opportunities, then bone marrow biopsy should be performed. It should also be performed when cytotoxic therapy was initiated before PET/CT could be done. This is a weak recommendation supported by moderate evidence.

Since patients with PMBCL are usually young adults at presentation, it’s important to consider fertility preservation in the face of chemotherapy. For males, semen preservation should be offered. Female patients may not be able to postpone treatment long enough to accomplish egg harvesting. The risk of infertility and premature ovarian failure will depend on the treatment regimen, so “the risks of each individual therapeutic regimen should be discussed with the patient,” Dr. Cwynarski and her colleagues said.

If a patient is diagnosed with PMBCL while pregnant, treatment should be managed in conjunction with high-risk obstetrics and anesthesia specialists. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used in pregnancy, and immunotherapy without antimetabolites can be considered in the second and third trimesters, according to the good practice paper. These are strong fertility and pregnancy recommendations, backed by moderate to low-quality evidence.

If superior vena cava obstruction causes thrombosis, local standard of care for anticoagulation should be used, but therapy-induced thrombocytopenia should be taken into consideration.

There is a lack of prospective, randomized studies to guide treatment decisions in PMBCL, according to the paper. Still, adding rituximab improves both response rates and duration of remission, they noted.

The standard of care for treatment is six cycles of R-CHOP and involved site radiotherapy (ISRT). If the patient is being cared for at a site that can manage the complexities of dose adjustment and monitoring, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) without ISRT is an alternative, according to the good practice paper.

All patients should be offered clinical trial participation when feasible, a strong recommendation based on high-quality evidence.

To assess the response to therapy, R-CHOP and ISRT recipients not participating in a clinical trial should receive a PET-CT scan 2-3 months after treatment is completed, and DA-EPOCH-R patients should receive their scan 6 weeks after the end of therapy. For all patients, Deauville criteria should be used in reporting response scan results. These strong recommendations about posttherapy imaging are based on moderate-quality evidence.

The rate of relapse and refractory disease is relatively low at about 10%-30%, Dr. Cwynarski and her colleagues said. Relapse usually happens within the first year and is rare after 2 years; extranodal disease is common, but usually spares the central nervous system and bone marrow. The good practice paper authors strongly recommend, based on high-quality evidence, that biopsy and fluorodeoxyglucose-PET/CT should be performed with relapse.

Radiotherapy can be considered if the relapse is localized and the patient didn’t receive initial radiotherapy, a strong recommendation with moderate evidence to support it.

Salvage regimens for patients who have not previously achieved complete metabolic response lack a disease-specific evidence base, noted Dr. Cwynarski and her colleagues. Taking this into consideration, a PMBCL salvage regimen should be the same as that offered to patients with relapsed diffused large B-cell lymphoma. High-dose therapy and autologous stem cell transplantation is appropriate for responsive disease.

If radiotherapy had not been given previously, it should be considered either pre- or post transplant. This, along with the other salvage therapy guidance, is a weak recommendation, backed by moderate evidence.

For longer-term follow-up, asymptomatic patients should not have routine imaging, a strong recommendation with moderate evidence. “[P]atients who remain in remission may be considered for discharge back to primary care,” Dr. Cwynarski and her coauthors said, making a weak recommendation based on low-quality evidence. Patients and their primary care providers should know about the potential for such long-term complications as cardiac toxicities and second malignancies.

koakes@mdedge.com

SOURCE: Cwynarski K et al. Br J Haematol. 2019 Jan 4. doi:10.1111/bjh.15731

Fertility preservation, imaging and radiotherapy guidelines, and best practices in relapse or salvage therapy for primary mediastinal B-cell lymphoma (PMBCL) are all highlighted in a new good practice paper from the British Society for Haematology.

Though PMBCL was previously thought of as a subtype of diffuse large B-cell lymphoma, “gene expression profiling data has shown it to be a separate clinicopathological entity with evidence of an overlap with classic Hodgkin lymphoma,” said Kate Cwynarski, MD, PhD, of University College London Hospitals NHS Foundation Trust in England, and her coauthors. The recommendations were published in the British Journal of Haematology.

PMBCL makes up 2%-4% of non-Hodgkin lymphomas, they said; a bulky anterior mediastinal mass is the usual initial presentation. PMBCL does not usually spread beyond the thoracic cavity.

Biopsy, which should be reviewed by a hematopathologist, is required for a histological diagnosis of PMBCL. A multidisciplinary team should review the clinical presentation, pathology, and management plan, according to the good practice paper authors. This was a strong recommendation backed by a high level of evidence.

In addition, patients should receive positron emission tomography–computed tomography (PET/CT) at diagnosis, before steroids are administered, if possible, as standard of care. Results from the PET/CT should be reported in accordance with international guidelines. These strong recommendations are backed by high-quality evidence.

If PET/CT is performed, then “a bone marrow biopsy is not considered essential,” said Dr. Cwynarski and her coauthors. However, if the findings would influence management, such as when there is extranodal disease that presents central nervous system opportunities, then bone marrow biopsy should be performed. It should also be performed when cytotoxic therapy was initiated before PET/CT could be done. This is a weak recommendation supported by moderate evidence.

Since patients with PMBCL are usually young adults at presentation, it’s important to consider fertility preservation in the face of chemotherapy. For males, semen preservation should be offered. Female patients may not be able to postpone treatment long enough to accomplish egg harvesting. The risk of infertility and premature ovarian failure will depend on the treatment regimen, so “the risks of each individual therapeutic regimen should be discussed with the patient,” Dr. Cwynarski and her colleagues said.

If a patient is diagnosed with PMBCL while pregnant, treatment should be managed in conjunction with high-risk obstetrics and anesthesia specialists. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used in pregnancy, and immunotherapy without antimetabolites can be considered in the second and third trimesters, according to the good practice paper. These are strong fertility and pregnancy recommendations, backed by moderate to low-quality evidence.

If superior vena cava obstruction causes thrombosis, local standard of care for anticoagulation should be used, but therapy-induced thrombocytopenia should be taken into consideration.

There is a lack of prospective, randomized studies to guide treatment decisions in PMBCL, according to the paper. Still, adding rituximab improves both response rates and duration of remission, they noted.

The standard of care for treatment is six cycles of R-CHOP and involved site radiotherapy (ISRT). If the patient is being cared for at a site that can manage the complexities of dose adjustment and monitoring, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) without ISRT is an alternative, according to the good practice paper.

All patients should be offered clinical trial participation when feasible, a strong recommendation based on high-quality evidence.

To assess the response to therapy, R-CHOP and ISRT recipients not participating in a clinical trial should receive a PET-CT scan 2-3 months after treatment is completed, and DA-EPOCH-R patients should receive their scan 6 weeks after the end of therapy. For all patients, Deauville criteria should be used in reporting response scan results. These strong recommendations about posttherapy imaging are based on moderate-quality evidence.

The rate of relapse and refractory disease is relatively low at about 10%-30%, Dr. Cwynarski and her colleagues said. Relapse usually happens within the first year and is rare after 2 years; extranodal disease is common, but usually spares the central nervous system and bone marrow. The good practice paper authors strongly recommend, based on high-quality evidence, that biopsy and fluorodeoxyglucose-PET/CT should be performed with relapse.

Radiotherapy can be considered if the relapse is localized and the patient didn’t receive initial radiotherapy, a strong recommendation with moderate evidence to support it.

Salvage regimens for patients who have not previously achieved complete metabolic response lack a disease-specific evidence base, noted Dr. Cwynarski and her colleagues. Taking this into consideration, a PMBCL salvage regimen should be the same as that offered to patients with relapsed diffused large B-cell lymphoma. High-dose therapy and autologous stem cell transplantation is appropriate for responsive disease.

If radiotherapy had not been given previously, it should be considered either pre- or post transplant. This, along with the other salvage therapy guidance, is a weak recommendation, backed by moderate evidence.

For longer-term follow-up, asymptomatic patients should not have routine imaging, a strong recommendation with moderate evidence. “[P]atients who remain in remission may be considered for discharge back to primary care,” Dr. Cwynarski and her coauthors said, making a weak recommendation based on low-quality evidence. Patients and their primary care providers should know about the potential for such long-term complications as cardiac toxicities and second malignancies.

koakes@mdedge.com

SOURCE: Cwynarski K et al. Br J Haematol. 2019 Jan 4. doi:10.1111/bjh.15731

This time of year the nonclinical medical journals are full of articles with titles like “Make This Your Best Financial Year!”

pinkomelet/Thinkstock

I read them January after January, but each year they remind me less of January 1st and more of February 2nd – Groundhog Day.

It seems you could republish the same article every year and change the title. All of them mention “collect patient copays” and “submit insurance billings promptly.” I had no idea some offices don’t. To me, this is like suggesting I pay my mortgage each month as a financial tip.

They inevitably also talk about improving my “web presence.” Most small practices don’t have an IT department. I’m it here. My modest (and that’s an exaggeration) web page has a 2003 picture of me that I desperately need to update but don’t have the time or expertise to do these days. People seem to think that small practices are wallowing in time and money, but realistically we have neither.

They also highlight all the free things we can do on the web, like a blog or Twitter account, to promote a practice. They fail to realize how much time it takes to regularly write a blog post. Twitter posts from most practices are either tripe such as “Remember – our office will be closed on Christmas!” or links to some recently published study about the importance of diet and exercise.

Besides, in this day and age pretty much anything can be taken as a claim of a doctor-patient relationship. There’s always someone looking to claim your seemingly innocuous blog post constituted harmful medical advice and try to sue you.

Turn my scheduling over to an online program for greater efficiency? No thanks, I’ll leave that to my awesome secretary. After 15 years here, she knows my personality and can quickly screen out people who will be a bad match for me. She also knows our patients and has a good gestalt for figuring how much time certain people will need. This prevents me from getting too far off schedule. She may not be as efficient as an online booking program, but she’s far more valuable. I’ll take quality over quantity any day.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This time of year the nonclinical medical journals are full of articles with titles like “Make This Your Best Financial Year!”

pinkomelet/Thinkstock

I read them January after January, but each year they remind me less of January 1st and more of February 2nd – Groundhog Day.

It seems you could republish the same article every year and change the title. All of them mention “collect patient copays” and “submit insurance billings promptly.” I had no idea some offices don’t. To me, this is like suggesting I pay my mortgage each month as a financial tip.

They inevitably also talk about improving my “web presence.” Most small practices don’t have an IT department. I’m it here. My modest (and that’s an exaggeration) web page has a 2003 picture of me that I desperately need to update but don’t have the time or expertise to do these days. People seem to think that small practices are wallowing in time and money, but realistically we have neither.

They also highlight all the free things we can do on the web, like a blog or Twitter account, to promote a practice. They fail to realize how much time it takes to regularly write a blog post. Twitter posts from most practices are either tripe such as “Remember – our office will be closed on Christmas!” or links to some recently published study about the importance of diet and exercise.

Besides, in this day and age pretty much anything can be taken as a claim of a doctor-patient relationship. There’s always someone looking to claim your seemingly innocuous blog post constituted harmful medical advice and try to sue you.

Turn my scheduling over to an online program for greater efficiency? No thanks, I’ll leave that to my awesome secretary. After 15 years here, she knows my personality and can quickly screen out people who will be a bad match for me. She also knows our patients and has a good gestalt for figuring how much time certain people will need. This prevents me from getting too far off schedule. She may not be as efficient as an online booking program, but she’s far more valuable. I’ll take quality over quantity any day.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This time of year the nonclinical medical journals are full of articles with titles like “Make This Your Best Financial Year!”

pinkomelet/Thinkstock

I read them January after January, but each year they remind me less of January 1st and more of February 2nd – Groundhog Day.

It seems you could republish the same article every year and change the title. All of them mention “collect patient copays” and “submit insurance billings promptly.” I had no idea some offices don’t. To me, this is like suggesting I pay my mortgage each month as a financial tip.

They inevitably also talk about improving my “web presence.” Most small practices don’t have an IT department. I’m it here. My modest (and that’s an exaggeration) web page has a 2003 picture of me that I desperately need to update but don’t have the time or expertise to do these days. People seem to think that small practices are wallowing in time and money, but realistically we have neither.

They also highlight all the free things we can do on the web, like a blog or Twitter account, to promote a practice. They fail to realize how much time it takes to regularly write a blog post. Twitter posts from most practices are either tripe such as “Remember – our office will be closed on Christmas!” or links to some recently published study about the importance of diet and exercise.

Besides, in this day and age pretty much anything can be taken as a claim of a doctor-patient relationship. There’s always someone looking to claim your seemingly innocuous blog post constituted harmful medical advice and try to sue you.

Turn my scheduling over to an online program for greater efficiency? No thanks, I’ll leave that to my awesome secretary. After 15 years here, she knows my personality and can quickly screen out people who will be a bad match for me. She also knows our patients and has a good gestalt for figuring how much time certain people will need. This prevents me from getting too far off schedule. She may not be as efficient as an online booking program, but she’s far more valuable. I’ll take quality over quantity any day.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

PARIS – The more comorbid conditions present in patients with moderate to severe plaque psoriasis, the less likely they are to achieve complete clearance in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.

Bruce Jancin/MDedge News

“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.

The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.

Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.

The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.

Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.

During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.

The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.

Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.

The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.

The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.

bjancin@mdedge.com

SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.

PARIS – The more comorbid conditions present in patients with moderate to severe plaque psoriasis, the less likely they are to achieve complete clearance in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.

Bruce Jancin/MDedge News

“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.

The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.

Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.

The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.

Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.

During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.

The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.

Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.

The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.

The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.

bjancin@mdedge.com

SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.

PARIS – The more comorbid conditions present in patients with moderate to severe plaque psoriasis, the less likely they are to achieve complete clearance in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.

Bruce Jancin/MDedge News

“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.

The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.

Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.

The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.

Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.

During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.

The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.

Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.

The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.

The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.

bjancin@mdedge.com

SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.

SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify