The Supreme Court on Tuesday will hear oral arguments in a case that, for the third time in eight years, could result in the justices striking down the Affordable Care Act.

ETIENJones/thinkstockphotos

The case, California v. Texas, is the result of a change to the health law made by Congress in 2017. As part of a major tax bill, Congress reduced to zero the penalty for not having health insurance. But it was that penalty – a tax – that the high court ruled made the law constitutional in a 2012 decision, argues a group of Republican state attorneys general. Without the tax, they say in their suit, the rest of the law must fall, too.

After originally contending that the entire law should not be struck down when the suit was filed in 2018, the Trump administration changed course in 2019 and joined the GOP officials who brought the case.

Here are some key questions and answers about the case.
 

What are the possibilities for how the court could rule?

There is a long list of ways this could play out.

The justices could declare the entire law unconstitutional – which is what a federal district judge in Texas ruled in December 2018. But legal experts say that’s not the most likely outcome of this case.

First, the court may avoid deciding the case on its merits entirely by ruling that the plaintiffs do not have “standing” to sue. The central issue in the case is whether the requirement in the law to have insurance – which remains even though Congress eliminated the penalty or tax – is constitutional. But states are not subject to the so-called individual mandate, so some analysts suggest the Republican officials have no standing. In addition, questions have been raised about the individual plaintiffs in the case, two consultants from Texas who argue that they felt compelled to buy insurance even without a possible penalty.

The court could also rule that, by eliminating the penalty but not the rest of the mandate (which Congress could not do in that 2017 tax bill for procedural reasons), lawmakers “didn’t mean to coerce anyone to do anything, and so there’s no constitutional problem,” University of Michigan law professor Nicholas Bagley said in a recent webinar for the NIHCM Foundation, the Commonwealth Fund, and the University of Southern California’s Center for Health Journalism.

Or, said Bagley, the court could rule that, without the tax, the requirement to have health insurance is unconstitutional, but the rest of the law is not. In that case, the justices might strike the mandate only, which would have basically no impact.

It gets more complicated if the court decides that, as the plaintiffs argue, the individual mandate language without the penalty is unconstitutional and so closely tied to other parts of the law that some of them must fall as well.

Even there the court has choices. One option would be, as the Trump administration originally argued, to strike down the mandate and just the pieces of the law most closely related to it – which happen to include the insurance protections for people with preexisting conditions, an extremely popular provision of the law. The two parts are connected because the original purpose of the mandate was to make sure enough healthy people sign up for insurance to offset the added costs to insurers of sicker people.

Another option, of course, would be for the court to follow the lead of the Texas judge and strike down the entire law.

While that’s not the most likely outcome, said Bagley, if it happens it could be “a hot mess” for the nation’s entire health care system. As just one example, he said, “every hospital is getting paid pursuant to changes made by the ACA. How do you even go about making payments if the thing that you are looking to guide what those payments ought to be is itself invalid?”
 

What impact will new Justice Amy Coney Barrett have?

Perhaps a lot. Before the death of Justice Ruth Bader Ginsburg, most court observers thought the case was highly unlikely to result in the entire law being struck down. That’s because Chief Justice John Roberts voted to uphold the law in 2012, and again when it was challenged in a less sweeping way in 2015.

But with Barrett replacing Ginsburg, even if Roberts joined the court’s remaining three liberals they could still be outvoted by the other five conservatives. Barrett was coy about her views on the Affordable Care Act during her confirmation hearings in October, but she has written that she thinks Roberts was wrong to uphold the law in 2012.
 

Could a new president and Congress make the case go away?

Many have suggested that, if Joe Biden assumes the presidency, his Justice Department could simply drop the case. But the administration did not bring the case; the GOP state officials did. And while normally the Justice Department’s job is to defend existing laws in court, in this case the ACA is being defended by a group of Democratic state attorneys general. A new administration could change that position, but that’s not the same as dropping the case.

Congress, on the other hand, could easily make the case moot. It could add back even a nominal financial penalty for not having insurance. It could eliminate the mandate altogether, although that would require 60 votes in the Senate under current rules. Congress could also pass a “severability” provision saying that, if any portion of the law is struck down, the rest should remain.

“The problem is not technical,” said Bagley. “It’s political.”
 

What is the timeline for a decision? Could the court delay implementation of its ruling?

The court usually hears oral arguments in a case months before it issues a decision. Unless the decision is unanimous or turns out to be very simple, Bagley said, he would expect to see an opinion “sometime in the spring.”

As to whether the court could find some or all of the law unconstitutional but delay when its decision takes effect, Bagley said that happened from time to time as recently as the 1970s. “That practice has been more or less abandoned,” he said, but in the case of a law so large, “you could imagine the Supreme Court using its discretion to say the decision wouldn’t take effect immediately.”

If the court does invalidate the entire ACA, Congress could act to fix things, but it’s unclear if it will be able to, especially if Republicans still control the Senate. If the justices strike the law, Bagley said, “I honestly think the likeliest outcome is that Congress runs around like a chicken with its head cut off, doesn’t come to a deal, and we’re back to where we were before 2010” when the ACA passed.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

The Supreme Court on Tuesday will hear oral arguments in a case that, for the third time in eight years, could result in the justices striking down the Affordable Care Act.

ETIENJones/thinkstockphotos

The case, California v. Texas, is the result of a change to the health law made by Congress in 2017. As part of a major tax bill, Congress reduced to zero the penalty for not having health insurance. But it was that penalty – a tax – that the high court ruled made the law constitutional in a 2012 decision, argues a group of Republican state attorneys general. Without the tax, they say in their suit, the rest of the law must fall, too.

After originally contending that the entire law should not be struck down when the suit was filed in 2018, the Trump administration changed course in 2019 and joined the GOP officials who brought the case.

Here are some key questions and answers about the case.
 

What are the possibilities for how the court could rule?

There is a long list of ways this could play out.

The justices could declare the entire law unconstitutional – which is what a federal district judge in Texas ruled in December 2018. But legal experts say that’s not the most likely outcome of this case.

First, the court may avoid deciding the case on its merits entirely by ruling that the plaintiffs do not have “standing” to sue. The central issue in the case is whether the requirement in the law to have insurance – which remains even though Congress eliminated the penalty or tax – is constitutional. But states are not subject to the so-called individual mandate, so some analysts suggest the Republican officials have no standing. In addition, questions have been raised about the individual plaintiffs in the case, two consultants from Texas who argue that they felt compelled to buy insurance even without a possible penalty.

The court could also rule that, by eliminating the penalty but not the rest of the mandate (which Congress could not do in that 2017 tax bill for procedural reasons), lawmakers “didn’t mean to coerce anyone to do anything, and so there’s no constitutional problem,” University of Michigan law professor Nicholas Bagley said in a recent webinar for the NIHCM Foundation, the Commonwealth Fund, and the University of Southern California’s Center for Health Journalism.

Or, said Bagley, the court could rule that, without the tax, the requirement to have health insurance is unconstitutional, but the rest of the law is not. In that case, the justices might strike the mandate only, which would have basically no impact.

It gets more complicated if the court decides that, as the plaintiffs argue, the individual mandate language without the penalty is unconstitutional and so closely tied to other parts of the law that some of them must fall as well.

Even there the court has choices. One option would be, as the Trump administration originally argued, to strike down the mandate and just the pieces of the law most closely related to it – which happen to include the insurance protections for people with preexisting conditions, an extremely popular provision of the law. The two parts are connected because the original purpose of the mandate was to make sure enough healthy people sign up for insurance to offset the added costs to insurers of sicker people.

Another option, of course, would be for the court to follow the lead of the Texas judge and strike down the entire law.

While that’s not the most likely outcome, said Bagley, if it happens it could be “a hot mess” for the nation’s entire health care system. As just one example, he said, “every hospital is getting paid pursuant to changes made by the ACA. How do you even go about making payments if the thing that you are looking to guide what those payments ought to be is itself invalid?”
 

What impact will new Justice Amy Coney Barrett have?

Perhaps a lot. Before the death of Justice Ruth Bader Ginsburg, most court observers thought the case was highly unlikely to result in the entire law being struck down. That’s because Chief Justice John Roberts voted to uphold the law in 2012, and again when it was challenged in a less sweeping way in 2015.

But with Barrett replacing Ginsburg, even if Roberts joined the court’s remaining three liberals they could still be outvoted by the other five conservatives. Barrett was coy about her views on the Affordable Care Act during her confirmation hearings in October, but she has written that she thinks Roberts was wrong to uphold the law in 2012.
 

Could a new president and Congress make the case go away?

Many have suggested that, if Joe Biden assumes the presidency, his Justice Department could simply drop the case. But the administration did not bring the case; the GOP state officials did. And while normally the Justice Department’s job is to defend existing laws in court, in this case the ACA is being defended by a group of Democratic state attorneys general. A new administration could change that position, but that’s not the same as dropping the case.

Congress, on the other hand, could easily make the case moot. It could add back even a nominal financial penalty for not having insurance. It could eliminate the mandate altogether, although that would require 60 votes in the Senate under current rules. Congress could also pass a “severability” provision saying that, if any portion of the law is struck down, the rest should remain.

“The problem is not technical,” said Bagley. “It’s political.”
 

What is the timeline for a decision? Could the court delay implementation of its ruling?

The court usually hears oral arguments in a case months before it issues a decision. Unless the decision is unanimous or turns out to be very simple, Bagley said, he would expect to see an opinion “sometime in the spring.”

As to whether the court could find some or all of the law unconstitutional but delay when its decision takes effect, Bagley said that happened from time to time as recently as the 1970s. “That practice has been more or less abandoned,” he said, but in the case of a law so large, “you could imagine the Supreme Court using its discretion to say the decision wouldn’t take effect immediately.”

If the court does invalidate the entire ACA, Congress could act to fix things, but it’s unclear if it will be able to, especially if Republicans still control the Senate. If the justices strike the law, Bagley said, “I honestly think the likeliest outcome is that Congress runs around like a chicken with its head cut off, doesn’t come to a deal, and we’re back to where we were before 2010” when the ACA passed.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

The Supreme Court on Tuesday will hear oral arguments in a case that, for the third time in eight years, could result in the justices striking down the Affordable Care Act.

ETIENJones/thinkstockphotos

The case, California v. Texas, is the result of a change to the health law made by Congress in 2017. As part of a major tax bill, Congress reduced to zero the penalty for not having health insurance. But it was that penalty – a tax – that the high court ruled made the law constitutional in a 2012 decision, argues a group of Republican state attorneys general. Without the tax, they say in their suit, the rest of the law must fall, too.

After originally contending that the entire law should not be struck down when the suit was filed in 2018, the Trump administration changed course in 2019 and joined the GOP officials who brought the case.

Here are some key questions and answers about the case.
 

What are the possibilities for how the court could rule?

There is a long list of ways this could play out.

The justices could declare the entire law unconstitutional – which is what a federal district judge in Texas ruled in December 2018. But legal experts say that’s not the most likely outcome of this case.

First, the court may avoid deciding the case on its merits entirely by ruling that the plaintiffs do not have “standing” to sue. The central issue in the case is whether the requirement in the law to have insurance – which remains even though Congress eliminated the penalty or tax – is constitutional. But states are not subject to the so-called individual mandate, so some analysts suggest the Republican officials have no standing. In addition, questions have been raised about the individual plaintiffs in the case, two consultants from Texas who argue that they felt compelled to buy insurance even without a possible penalty.

The court could also rule that, by eliminating the penalty but not the rest of the mandate (which Congress could not do in that 2017 tax bill for procedural reasons), lawmakers “didn’t mean to coerce anyone to do anything, and so there’s no constitutional problem,” University of Michigan law professor Nicholas Bagley said in a recent webinar for the NIHCM Foundation, the Commonwealth Fund, and the University of Southern California’s Center for Health Journalism.

Or, said Bagley, the court could rule that, without the tax, the requirement to have health insurance is unconstitutional, but the rest of the law is not. In that case, the justices might strike the mandate only, which would have basically no impact.

It gets more complicated if the court decides that, as the plaintiffs argue, the individual mandate language without the penalty is unconstitutional and so closely tied to other parts of the law that some of them must fall as well.

Even there the court has choices. One option would be, as the Trump administration originally argued, to strike down the mandate and just the pieces of the law most closely related to it – which happen to include the insurance protections for people with preexisting conditions, an extremely popular provision of the law. The two parts are connected because the original purpose of the mandate was to make sure enough healthy people sign up for insurance to offset the added costs to insurers of sicker people.

Another option, of course, would be for the court to follow the lead of the Texas judge and strike down the entire law.

While that’s not the most likely outcome, said Bagley, if it happens it could be “a hot mess” for the nation’s entire health care system. As just one example, he said, “every hospital is getting paid pursuant to changes made by the ACA. How do you even go about making payments if the thing that you are looking to guide what those payments ought to be is itself invalid?”
 

What impact will new Justice Amy Coney Barrett have?

Perhaps a lot. Before the death of Justice Ruth Bader Ginsburg, most court observers thought the case was highly unlikely to result in the entire law being struck down. That’s because Chief Justice John Roberts voted to uphold the law in 2012, and again when it was challenged in a less sweeping way in 2015.

But with Barrett replacing Ginsburg, even if Roberts joined the court’s remaining three liberals they could still be outvoted by the other five conservatives. Barrett was coy about her views on the Affordable Care Act during her confirmation hearings in October, but she has written that she thinks Roberts was wrong to uphold the law in 2012.
 

Could a new president and Congress make the case go away?

Many have suggested that, if Joe Biden assumes the presidency, his Justice Department could simply drop the case. But the administration did not bring the case; the GOP state officials did. And while normally the Justice Department’s job is to defend existing laws in court, in this case the ACA is being defended by a group of Democratic state attorneys general. A new administration could change that position, but that’s not the same as dropping the case.

Congress, on the other hand, could easily make the case moot. It could add back even a nominal financial penalty for not having insurance. It could eliminate the mandate altogether, although that would require 60 votes in the Senate under current rules. Congress could also pass a “severability” provision saying that, if any portion of the law is struck down, the rest should remain.

“The problem is not technical,” said Bagley. “It’s political.”
 

What is the timeline for a decision? Could the court delay implementation of its ruling?

The court usually hears oral arguments in a case months before it issues a decision. Unless the decision is unanimous or turns out to be very simple, Bagley said, he would expect to see an opinion “sometime in the spring.”

As to whether the court could find some or all of the law unconstitutional but delay when its decision takes effect, Bagley said that happened from time to time as recently as the 1970s. “That practice has been more or less abandoned,” he said, but in the case of a law so large, “you could imagine the Supreme Court using its discretion to say the decision wouldn’t take effect immediately.”

If the court does invalidate the entire ACA, Congress could act to fix things, but it’s unclear if it will be able to, especially if Republicans still control the Senate. If the justices strike the law, Bagley said, “I honestly think the likeliest outcome is that Congress runs around like a chicken with its head cut off, doesn’t come to a deal, and we’re back to where we were before 2010” when the ACA passed.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Key clinical point: Fingolimod is superior to glatiramer acetate in reducing the relapse rates for relapsing-remitting multiple sclerosis (RRMS), and 0.5 mg is the optimal dose.

Major finding: Fingolimod 0.5 mg vs. glatiramer acetate treatment showed a 40.7% relative reduction in annualized relapse rate (P = .01). No statistically significant difference was seen with fingolimod 0.25 mg vs. glatiramer acetate (14.6% reduction in annualized relapse rate; P = .42).

Study details: Phase 3b ASSESS trial: Patients with RRMS were randomly assigned to fingolimod 0.5 mg (n = 352), fingolimod 0.25 mg (n = 370), or to glatiramer acetate 20 mg (n = 342) groups for 12 months.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. The authors reported ties with various pharmaceutical companies, including Novartis.

Citation: Cree BAC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2950

Key clinical point: Fingolimod is superior to glatiramer acetate in reducing the relapse rates for relapsing-remitting multiple sclerosis (RRMS), and 0.5 mg is the optimal dose.

Major finding: Fingolimod 0.5 mg vs. glatiramer acetate treatment showed a 40.7% relative reduction in annualized relapse rate (P = .01). No statistically significant difference was seen with fingolimod 0.25 mg vs. glatiramer acetate (14.6% reduction in annualized relapse rate; P = .42).

Study details: Phase 3b ASSESS trial: Patients with RRMS were randomly assigned to fingolimod 0.5 mg (n = 352), fingolimod 0.25 mg (n = 370), or to glatiramer acetate 20 mg (n = 342) groups for 12 months.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. The authors reported ties with various pharmaceutical companies, including Novartis.

Citation: Cree BAC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2950

Key clinical point: Fingolimod is superior to glatiramer acetate in reducing the relapse rates for relapsing-remitting multiple sclerosis (RRMS), and 0.5 mg is the optimal dose.

Major finding: Fingolimod 0.5 mg vs. glatiramer acetate treatment showed a 40.7% relative reduction in annualized relapse rate (P = .01). No statistically significant difference was seen with fingolimod 0.25 mg vs. glatiramer acetate (14.6% reduction in annualized relapse rate; P = .42).

Study details: Phase 3b ASSESS trial: Patients with RRMS were randomly assigned to fingolimod 0.5 mg (n = 352), fingolimod 0.25 mg (n = 370), or to glatiramer acetate 20 mg (n = 342) groups for 12 months.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. The authors reported ties with various pharmaceutical companies, including Novartis.

Citation: Cree BAC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2950

Key clinical point: This meta-analysis suggests that the risk for cancer in patients with multiple sclerosis (MS) is less than the general population.

Major finding: The pooled relative risk (RR) of developing cancer was estimated as 0.83 (P less than .001), which shows that risk for cancer was 17% less in patients with MS than the general population. The RR of developing cancer in MS individuals differed between studies ranging from 0.7 to 1.67.

Study details: A systematic review and meta-analysis of 5 studies.

Disclosures: The study received no funding. The authors declared no conflicts of interest.

Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Aug 13. doi: 10.1016/j.autrev.2020.102650.

Key clinical point: This meta-analysis suggests that the risk for cancer in patients with multiple sclerosis (MS) is less than the general population.

Major finding: The pooled relative risk (RR) of developing cancer was estimated as 0.83 (P less than .001), which shows that risk for cancer was 17% less in patients with MS than the general population. The RR of developing cancer in MS individuals differed between studies ranging from 0.7 to 1.67.

Study details: A systematic review and meta-analysis of 5 studies.

Disclosures: The study received no funding. The authors declared no conflicts of interest.

Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Aug 13. doi: 10.1016/j.autrev.2020.102650.

Key clinical point: This meta-analysis suggests that the risk for cancer in patients with multiple sclerosis (MS) is less than the general population.

Major finding: The pooled relative risk (RR) of developing cancer was estimated as 0.83 (P less than .001), which shows that risk for cancer was 17% less in patients with MS than the general population. The RR of developing cancer in MS individuals differed between studies ranging from 0.7 to 1.67.

Study details: A systematic review and meta-analysis of 5 studies.

Disclosures: The study received no funding. The authors declared no conflicts of interest.

Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Aug 13. doi: 10.1016/j.autrev.2020.102650.

Key clinical point: Cladribine tablets had lower annualized relapse rate (ARR) vs. interferon, glatiramer acetate, and dimethyl fumarate for relapsing-remitting multiple sclerosis (RRMS) in the first 2 years; a similar ARR vs. fingolimod; and a higher ARR vs. natalizumab.

Major finding: Cladribine demonstrated significantly lower ARR vs. interferon (relapse ratio [RR], 0.48; P less than .001), glatiramer acetate (RR, 0.49; P less than .001), and dimethyl fumarate (RR, 0.6; P = .001). No significant differences in ARR were observed when compared with fingolimod (RR = 0.74; P = .24), whereas higher ARR was observed vs. natalizumab (RR, 2.13; P = .014).

Study details: This study compared the efficacy of cladribine vs. other approved drugs in patients with RRMS by matching randomized controlled trial (CLARITY trial; cladribine tablets vs. placebo; n = 945) to observational data (Italian multicenter database i-MuST; n = 2,204).

Disclosures: The study was sponsored by Merck Serono S.p.A., Rome, Italy; an affiliate of Merck KGaA, Darmstadt, Germany. Dr. Signori had no disclosures. Dr. Visconti is an employee at Merck Serono, Italy, and Dr. Sormani received consulting fees from various pharmaceutical companies including Merck KGaA.

Citation: Signori A et al. Neurol Neuroimmunol Neuroinflamm. 2020 Aug 14. doi: 10.1212/NXI.0000000000000878.

Key clinical point: Cladribine tablets had lower annualized relapse rate (ARR) vs. interferon, glatiramer acetate, and dimethyl fumarate for relapsing-remitting multiple sclerosis (RRMS) in the first 2 years; a similar ARR vs. fingolimod; and a higher ARR vs. natalizumab.

Major finding: Cladribine demonstrated significantly lower ARR vs. interferon (relapse ratio [RR], 0.48; P less than .001), glatiramer acetate (RR, 0.49; P less than .001), and dimethyl fumarate (RR, 0.6; P = .001). No significant differences in ARR were observed when compared with fingolimod (RR = 0.74; P = .24), whereas higher ARR was observed vs. natalizumab (RR, 2.13; P = .014).

Study details: This study compared the efficacy of cladribine vs. other approved drugs in patients with RRMS by matching randomized controlled trial (CLARITY trial; cladribine tablets vs. placebo; n = 945) to observational data (Italian multicenter database i-MuST; n = 2,204).

Disclosures: The study was sponsored by Merck Serono S.p.A., Rome, Italy; an affiliate of Merck KGaA, Darmstadt, Germany. Dr. Signori had no disclosures. Dr. Visconti is an employee at Merck Serono, Italy, and Dr. Sormani received consulting fees from various pharmaceutical companies including Merck KGaA.

Citation: Signori A et al. Neurol Neuroimmunol Neuroinflamm. 2020 Aug 14. doi: 10.1212/NXI.0000000000000878.

Key clinical point: Cladribine tablets had lower annualized relapse rate (ARR) vs. interferon, glatiramer acetate, and dimethyl fumarate for relapsing-remitting multiple sclerosis (RRMS) in the first 2 years; a similar ARR vs. fingolimod; and a higher ARR vs. natalizumab.

Major finding: Cladribine demonstrated significantly lower ARR vs. interferon (relapse ratio [RR], 0.48; P less than .001), glatiramer acetate (RR, 0.49; P less than .001), and dimethyl fumarate (RR, 0.6; P = .001). No significant differences in ARR were observed when compared with fingolimod (RR = 0.74; P = .24), whereas higher ARR was observed vs. natalizumab (RR, 2.13; P = .014).

Study details: This study compared the efficacy of cladribine vs. other approved drugs in patients with RRMS by matching randomized controlled trial (CLARITY trial; cladribine tablets vs. placebo; n = 945) to observational data (Italian multicenter database i-MuST; n = 2,204).

Disclosures: The study was sponsored by Merck Serono S.p.A., Rome, Italy; an affiliate of Merck KGaA, Darmstadt, Germany. Dr. Signori had no disclosures. Dr. Visconti is an employee at Merck Serono, Italy, and Dr. Sormani received consulting fees from various pharmaceutical companies including Merck KGaA.

Citation: Signori A et al. Neurol Neuroimmunol Neuroinflamm. 2020 Aug 14. doi: 10.1212/NXI.0000000000000878.

Key clinical point: Pregnancy and childbirth seem to delay the onset of multiple sclerosis by more than 3 years. However, having more pregnancies is not associated with later onset.

Major finding: Onset of clinically isolated syndrome (CIS) was later in women with previous pregnancies and childbirths vs. those without pregnancies and childbirths (hazard ratio, 0.68; P less than .001), with a median delay of 3.3 years. No association was seen between higher number of pregnancies and childbirths and delay in CIS onset.

Study details: The findings are based on a multicenter cohort study of 2,557 women with CIS (mean age at CIS onset, 31.5 years) from the MSBase Registry.

Disclosures: The study was supported by a postgraduate scholarship and Ian Ballard Travel Award from MS Research Australia, an Australian Government Research Training Program Scholarship, and a grant from the National Health and Medical Research Council. The lead author reported receiving grants from MS Research Australia during the conduct of the study; grants, personal fees, and nonfinancial support from Biogen; grants and personal fees from Merck Serono; personal fees from Teva and Novartis; and nonfinancial support from Roche and Genzyme-Sanofi outside the submitted work.

Citation: Nguyen AL et al. JAMA Neurol. 2020 Sep 14. doi: 10.1001/jamaneurol.2020.3324.

Key clinical point: Pregnancy and childbirth seem to delay the onset of multiple sclerosis by more than 3 years. However, having more pregnancies is not associated with later onset.

Major finding: Onset of clinically isolated syndrome (CIS) was later in women with previous pregnancies and childbirths vs. those without pregnancies and childbirths (hazard ratio, 0.68; P less than .001), with a median delay of 3.3 years. No association was seen between higher number of pregnancies and childbirths and delay in CIS onset.

Study details: The findings are based on a multicenter cohort study of 2,557 women with CIS (mean age at CIS onset, 31.5 years) from the MSBase Registry.

Disclosures: The study was supported by a postgraduate scholarship and Ian Ballard Travel Award from MS Research Australia, an Australian Government Research Training Program Scholarship, and a grant from the National Health and Medical Research Council. The lead author reported receiving grants from MS Research Australia during the conduct of the study; grants, personal fees, and nonfinancial support from Biogen; grants and personal fees from Merck Serono; personal fees from Teva and Novartis; and nonfinancial support from Roche and Genzyme-Sanofi outside the submitted work.

Citation: Nguyen AL et al. JAMA Neurol. 2020 Sep 14. doi: 10.1001/jamaneurol.2020.3324.

Key clinical point: Pregnancy and childbirth seem to delay the onset of multiple sclerosis by more than 3 years. However, having more pregnancies is not associated with later onset.

Major finding: Onset of clinically isolated syndrome (CIS) was later in women with previous pregnancies and childbirths vs. those without pregnancies and childbirths (hazard ratio, 0.68; P less than .001), with a median delay of 3.3 years. No association was seen between higher number of pregnancies and childbirths and delay in CIS onset.

Study details: The findings are based on a multicenter cohort study of 2,557 women with CIS (mean age at CIS onset, 31.5 years) from the MSBase Registry.

Disclosures: The study was supported by a postgraduate scholarship and Ian Ballard Travel Award from MS Research Australia, an Australian Government Research Training Program Scholarship, and a grant from the National Health and Medical Research Council. The lead author reported receiving grants from MS Research Australia during the conduct of the study; grants, personal fees, and nonfinancial support from Biogen; grants and personal fees from Merck Serono; personal fees from Teva and Novartis; and nonfinancial support from Roche and Genzyme-Sanofi outside the submitted work.

Citation: Nguyen AL et al. JAMA Neurol. 2020 Sep 14. doi: 10.1001/jamaneurol.2020.3324.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

The Fitzpatrick Skin Typing system could use a makeover.

Even though the popular classification system added skin types V and VI in 1988 to the first iteration established in 1975, it was never intended for categorizing skin color, according to Karen C. Kagha, MD.

“This topic is going to become more relevant in our clinical practices, especially when you look at the current population trends in the U.S.,” Dr. Kagha, MD, a dermatologist and cosmetic and laser fellow in the department of dermatology at Massachusetts General Hospital and a research fellow at Wellman Center for Photomedicine, both in Boston, said during a virtual course on laser and aesthetic skin therapy. “Minority groups continue to increase. According to the U.S. Census Bureau, by the year 2050, we can expect that the majority of the population will be of non-European descent.”

The original intent of the Fitzpatrick Skin Typing (FST) system was to establish a minimal erythema dose, or likelihood to burn for patients receiving phototherapy, she continued. However, a recently published survey of 141 board-certified dermatologists and trainees found that 31% of respondents said that they used the Fitzpatrick Skin Typing System to describe the patient’s race or ethnicity, 47% used it to describe the patients’ constitutive skin color, and 22% used it in both scenarios.

She went on to postulate that there is likely “an infinite number of skin colors that are also impacted by geographic and cultural factors. Perhaps we should restructure how we think about skin typing. We need to establish a new consensus on skin typing, one that respects the variability in skin color but also one that’s clear, concise, objective, practical, and can be universally accepted.”

Dr. Kagha concluded her remarks by encouraging dermatologists to become more comfortable with treating all skin types. “This is going to be in line with the current population trends in the U.S., and also in line with the patients that we serve. Finally, I think we as physicians are in a unique position. Our patients’ frustrations and unsolved mysteries can drive our passion and our patient-centered innovation. For me, a common theme and a common source of frustration that I’ve seen in patients with increased melanin in their skin is figuring out how to effectively remove or prevent unwanted marks or unwanted pigment without disturbing the baseline pigment.”

Dr. Kagha reported having no financial disclosures.

dbrunk@mdedge.com

The Fitzpatrick Skin Typing system could use a makeover.

Even though the popular classification system added skin types V and VI in 1988 to the first iteration established in 1975, it was never intended for categorizing skin color, according to Karen C. Kagha, MD.

“This topic is going to become more relevant in our clinical practices, especially when you look at the current population trends in the U.S.,” Dr. Kagha, MD, a dermatologist and cosmetic and laser fellow in the department of dermatology at Massachusetts General Hospital and a research fellow at Wellman Center for Photomedicine, both in Boston, said during a virtual course on laser and aesthetic skin therapy. “Minority groups continue to increase. According to the U.S. Census Bureau, by the year 2050, we can expect that the majority of the population will be of non-European descent.”

The original intent of the Fitzpatrick Skin Typing (FST) system was to establish a minimal erythema dose, or likelihood to burn for patients receiving phototherapy, she continued. However, a recently published survey of 141 board-certified dermatologists and trainees found that 31% of respondents said that they used the Fitzpatrick Skin Typing System to describe the patient’s race or ethnicity, 47% used it to describe the patients’ constitutive skin color, and 22% used it in both scenarios.

She went on to postulate that there is likely “an infinite number of skin colors that are also impacted by geographic and cultural factors. Perhaps we should restructure how we think about skin typing. We need to establish a new consensus on skin typing, one that respects the variability in skin color but also one that’s clear, concise, objective, practical, and can be universally accepted.”

Dr. Kagha concluded her remarks by encouraging dermatologists to become more comfortable with treating all skin types. “This is going to be in line with the current population trends in the U.S., and also in line with the patients that we serve. Finally, I think we as physicians are in a unique position. Our patients’ frustrations and unsolved mysteries can drive our passion and our patient-centered innovation. For me, a common theme and a common source of frustration that I’ve seen in patients with increased melanin in their skin is figuring out how to effectively remove or prevent unwanted marks or unwanted pigment without disturbing the baseline pigment.”

Dr. Kagha reported having no financial disclosures.

dbrunk@mdedge.com

The Fitzpatrick Skin Typing system could use a makeover.

Even though the popular classification system added skin types V and VI in 1988 to the first iteration established in 1975, it was never intended for categorizing skin color, according to Karen C. Kagha, MD.

“This topic is going to become more relevant in our clinical practices, especially when you look at the current population trends in the U.S.,” Dr. Kagha, MD, a dermatologist and cosmetic and laser fellow in the department of dermatology at Massachusetts General Hospital and a research fellow at Wellman Center for Photomedicine, both in Boston, said during a virtual course on laser and aesthetic skin therapy. “Minority groups continue to increase. According to the U.S. Census Bureau, by the year 2050, we can expect that the majority of the population will be of non-European descent.”

The original intent of the Fitzpatrick Skin Typing (FST) system was to establish a minimal erythema dose, or likelihood to burn for patients receiving phototherapy, she continued. However, a recently published survey of 141 board-certified dermatologists and trainees found that 31% of respondents said that they used the Fitzpatrick Skin Typing System to describe the patient’s race or ethnicity, 47% used it to describe the patients’ constitutive skin color, and 22% used it in both scenarios.

She went on to postulate that there is likely “an infinite number of skin colors that are also impacted by geographic and cultural factors. Perhaps we should restructure how we think about skin typing. We need to establish a new consensus on skin typing, one that respects the variability in skin color but also one that’s clear, concise, objective, practical, and can be universally accepted.”

Dr. Kagha concluded her remarks by encouraging dermatologists to become more comfortable with treating all skin types. “This is going to be in line with the current population trends in the U.S., and also in line with the patients that we serve. Finally, I think we as physicians are in a unique position. Our patients’ frustrations and unsolved mysteries can drive our passion and our patient-centered innovation. For me, a common theme and a common source of frustration that I’ve seen in patients with increased melanin in their skin is figuring out how to effectively remove or prevent unwanted marks or unwanted pigment without disturbing the baseline pigment.”

Dr. Kagha reported having no financial disclosures.

dbrunk@mdedge.com

A genomic study has revealed new insights into the pathogenesis of neuroblastoma as well as potential therapeutic targets.

Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.

“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.

The group’s findings were published in Nature Communications.

The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.

The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).

MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).

“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.

Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.

Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.

“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.

Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.

“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.

The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.

SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.

A genomic study has revealed new insights into the pathogenesis of neuroblastoma as well as potential therapeutic targets.

Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.

“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.

The group’s findings were published in Nature Communications.

The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.

The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).

MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).

“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.

Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.

Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.

“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.

Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.

“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.

The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.

SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.

A genomic study has revealed new insights into the pathogenesis of neuroblastoma as well as potential therapeutic targets.

Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.

“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.

The group’s findings were published in Nature Communications.

The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.

The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).

MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).

“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.

Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.

Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.

“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.

Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.

“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.

The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.

SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.

Among young patients with severe obesity and disordered eating behaviors – continuous eating, overeating, and binge eating – those who had bariatric surgery saw an improvement in the eating behaviors.

Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.

Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.

At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.

Six years later, rates of disordered eating were much lower in those who had bariatric surgery.

The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.

“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
 

Robust findings because of long follow-up and controls

The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.

In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”

Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”

However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
 

How does bariatric surgery impact overeating, binge eating, in teens?

“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.

However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.

To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.

The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).

Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.

At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).

At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).

At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).  

Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
 

Disordered eating associated with low self-worth, anxiety, and depression

In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.

“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.

“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”

Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).

The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.  

A version of this article originally appeared on Medscape.com.

Among young patients with severe obesity and disordered eating behaviors – continuous eating, overeating, and binge eating – those who had bariatric surgery saw an improvement in the eating behaviors.

Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.

Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.

At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.

Six years later, rates of disordered eating were much lower in those who had bariatric surgery.

The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.

“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
 

Robust findings because of long follow-up and controls

The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.

In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”

Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”

However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
 

How does bariatric surgery impact overeating, binge eating, in teens?

“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.

However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.

To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.

The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).

Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.

At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).

At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).

At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).  

Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
 

Disordered eating associated with low self-worth, anxiety, and depression

In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.

“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.

“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”

Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).

The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.  

A version of this article originally appeared on Medscape.com.

Among young patients with severe obesity and disordered eating behaviors – continuous eating, overeating, and binge eating – those who had bariatric surgery saw an improvement in the eating behaviors.

Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.

Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.

At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.

Six years later, rates of disordered eating were much lower in those who had bariatric surgery.

The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.

“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
 

Robust findings because of long follow-up and controls

The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.

In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”

Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”

However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
 

How does bariatric surgery impact overeating, binge eating, in teens?

“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.

However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.

To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.

The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).

Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.

At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).

At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).

At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).  

Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
 

Disordered eating associated with low self-worth, anxiety, and depression

In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.

“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.

“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”

Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).

The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.  

A version of this article originally appeared on Medscape.com.