Guidelines

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

[email protected]

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

[email protected]

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

[email protected]

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

Gastroesophageal reflux (GER) is common in infants and often presents a challenge to doctors who try to balance changing evidence with concerns about complications and parents’ concerns about their infant’s discomfort. In a 2018 guideline, the writing committee defined GER as reflux of stomach contents to the esophagus. GER is considered pathologic and, therefore, gastroesophageal reflux disease (GERD) when it is associated with troublesome symptoms and/or complications that can include esophagitis and aspiration.

Infants

GERD is difficult to diagnose in infants. The symptoms of GERD, such as crying after feeds, regurgitation, and irritability, occur commonly in all infants and in any individual infant may not be reflective of GERD. Regurgitation is common, frequent and normal in infants up to 6 months of age. A common challenge occurs when families request treatment for infants with irritability, back arching, and/or regurgitation who are otherwise doing well. In this group of infants it is important to recognize that neither testing nor therapy is indicated unless there is difficulty with feeding, growth, acquisition of milestones, or red flag signs.

In infants with recurrent regurgitation history, physical exam is usually sufficient to distinguish uncomplicated GER from GERD and other more worrisome diagnoses. Red flag symptoms raise the possibility of a different diagnosis. Red flag symptoms include weight loss; lethargy; excessive irritability/pain; onset of vomiting for more than 6 months or persisting past 12-18 months of age; rapidly increasing head circumference; persistent forceful, nocturnal, bloody, or bilious vomiting; abdominal distention; rectal bleeding; and chronic diarrhea. GERD that starts after 6 months of age or which persists after 12 months of age warrants further evaluation, often with referral to a pediatric gastroenterologist.

When GERD is suspected, the first therapeutic steps are to institute behavioral changes. Caregivers should avoid overfeeding and modify the feeding pattern to more frequent feedings consisting of less volume at each feed. The addition of thickeners to feeds does reduce regurgitation, although it may not affect other GERD signs and symptoms. Formula can be thickened with rice cereal, which tends to be an affordable choice that doesn’t clog nipples. Enzymes present in breast milk digest cereal thickeners, so breast milk can be thickened with xanthum gum (after 1 year of age) or carob bean–based products (after 42 weeks gestation).

If these modifications do not improve symptoms, the next step is to change the type of feeds. Some infants in whom GERD is suspected actually have cow’s milk protein allergy (CMPA), so a trial of cow’s milk elimination is warranted. A breastfeeding mother can eliminate all dairy from her diet including casein and whey. Caregivers can switch to an extensively hydrolyzed formula or an amino acid–based formula. The guideline do not recommend soy-based formulas because they are not available in Europe and because a significant percentage of infants with CMPA also develop allergy to soy, and they do not recommend rice hydrolysate formula because of a lack of evidence. Dairy can be reintroduced at a later point. While positional changes including elevating the head of the crib or placing the infant in the left lateral position can help decrease GERD, the American Academy of Pediatrics strongly discourages these positions because of safety concerns, so the guidelines do not recommend positional change.

If a 2-4 week trial of nonpharmacologic interventions fails, the next step is referral to a pediatric gastroenterologist. If a pediatric gastroenterologist is not available, a 4-8 week trial of acid suppressive medication may be given. No trial has shown utility of a trial of acid suppression as a diagnostic test for GERD. Medication should only be used in infants with strongly suspected GERD and, per the guidelines, “should not be used for the treatment of visible regurgitation in otherwise healthy infants.” Medications to treat GER do not have evidence of efficacy, and there is evidence of an increased risk of infection with use of acid suppression, including an increased risk of necrotizing enterocolitis, pneumonia, upper respiratory tract infections, sepsis, urinary tract infections, and Clostridium difficile. If used, proton-pump inhibitors are preferred over histamine-2 receptor blockers. Antacids and alginates are not recommended.
 

Older children

In children with heartburn or regurgitation without red flag symptoms, a trial of lifestyle changes and dietary education may be initiated. If a child is overweight, it is important to inform the patient and parents that excess body weight is associated with GERD. The head of the bed can be elevated along with left lateral positioning. The guidelines do not support any probiotics or herbal medicines.

If bothersome symptoms persist, a trial of acid-suppressing medication for 4-8 weeks is reasonable. A PPI is preferred to a histamine-2 receptor blocker. PPI safety studies are lacking, but case studies suggest an increase in infections in children taking acid-suppressing medications. Therefore, as with infants, if medications are used they should be prescribed at the lowest dose and for the shortest period of time possible. If medications are not helping, or need to be used long term, referral to a pediatric gastroenterologist can be considered. Of note, the guidelines do support a 4-8 week trial of PPIs in older children as a diagnostic test; this differs from the recommendations for infants, in whom a trial for diagnostic purposes is discouraged.
 

Diagnostic testing

Refer to a gastroenterologist for endoscopy in cases of persistent symptoms despite PPI use or failure to wean off medication. If there are no erosions, pH monitoring with pH-impedance monitoring or pH-metry can help distinguish between nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. If it is performed when a child is off of PPIs, endoscopy can also diagnose PPI-responsive eosinophilic esophagitis. Barium contrast, abdominal ultrasonography, and manometry may be considered during the course of a search for an alternative diagnosis, but they should not be used to diagnose or confirm GERD.

The bottom line

Most GER is physiologic and does not need treatment. First-line treatment for GERD in infants and children is nonpharmacologic intervention.
 

Reference

Rosen R et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):516-554.

Dr. Oh is a third year resident in the Family Medicine Residency at Abington-Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Gastroesophageal reflux (GER) is common in infants and often presents a challenge to doctors who try to balance changing evidence with concerns about complications and parents’ concerns about their infant’s discomfort. In a 2018 guideline, the writing committee defined GER as reflux of stomach contents to the esophagus. GER is considered pathologic and, therefore, gastroesophageal reflux disease (GERD) when it is associated with troublesome symptoms and/or complications that can include esophagitis and aspiration.

Infants

GERD is difficult to diagnose in infants. The symptoms of GERD, such as crying after feeds, regurgitation, and irritability, occur commonly in all infants and in any individual infant may not be reflective of GERD. Regurgitation is common, frequent and normal in infants up to 6 months of age. A common challenge occurs when families request treatment for infants with irritability, back arching, and/or regurgitation who are otherwise doing well. In this group of infants it is important to recognize that neither testing nor therapy is indicated unless there is difficulty with feeding, growth, acquisition of milestones, or red flag signs.

In infants with recurrent regurgitation history, physical exam is usually sufficient to distinguish uncomplicated GER from GERD and other more worrisome diagnoses. Red flag symptoms raise the possibility of a different diagnosis. Red flag symptoms include weight loss; lethargy; excessive irritability/pain; onset of vomiting for more than 6 months or persisting past 12-18 months of age; rapidly increasing head circumference; persistent forceful, nocturnal, bloody, or bilious vomiting; abdominal distention; rectal bleeding; and chronic diarrhea. GERD that starts after 6 months of age or which persists after 12 months of age warrants further evaluation, often with referral to a pediatric gastroenterologist.

When GERD is suspected, the first therapeutic steps are to institute behavioral changes. Caregivers should avoid overfeeding and modify the feeding pattern to more frequent feedings consisting of less volume at each feed. The addition of thickeners to feeds does reduce regurgitation, although it may not affect other GERD signs and symptoms. Formula can be thickened with rice cereal, which tends to be an affordable choice that doesn’t clog nipples. Enzymes present in breast milk digest cereal thickeners, so breast milk can be thickened with xanthum gum (after 1 year of age) or carob bean–based products (after 42 weeks gestation).

If these modifications do not improve symptoms, the next step is to change the type of feeds. Some infants in whom GERD is suspected actually have cow’s milk protein allergy (CMPA), so a trial of cow’s milk elimination is warranted. A breastfeeding mother can eliminate all dairy from her diet including casein and whey. Caregivers can switch to an extensively hydrolyzed formula or an amino acid–based formula. The guideline do not recommend soy-based formulas because they are not available in Europe and because a significant percentage of infants with CMPA also develop allergy to soy, and they do not recommend rice hydrolysate formula because of a lack of evidence. Dairy can be reintroduced at a later point. While positional changes including elevating the head of the crib or placing the infant in the left lateral position can help decrease GERD, the American Academy of Pediatrics strongly discourages these positions because of safety concerns, so the guidelines do not recommend positional change.

If a 2-4 week trial of nonpharmacologic interventions fails, the next step is referral to a pediatric gastroenterologist. If a pediatric gastroenterologist is not available, a 4-8 week trial of acid suppressive medication may be given. No trial has shown utility of a trial of acid suppression as a diagnostic test for GERD. Medication should only be used in infants with strongly suspected GERD and, per the guidelines, “should not be used for the treatment of visible regurgitation in otherwise healthy infants.” Medications to treat GER do not have evidence of efficacy, and there is evidence of an increased risk of infection with use of acid suppression, including an increased risk of necrotizing enterocolitis, pneumonia, upper respiratory tract infections, sepsis, urinary tract infections, and Clostridium difficile. If used, proton-pump inhibitors are preferred over histamine-2 receptor blockers. Antacids and alginates are not recommended.
 

Older children

In children with heartburn or regurgitation without red flag symptoms, a trial of lifestyle changes and dietary education may be initiated. If a child is overweight, it is important to inform the patient and parents that excess body weight is associated with GERD. The head of the bed can be elevated along with left lateral positioning. The guidelines do not support any probiotics or herbal medicines.

If bothersome symptoms persist, a trial of acid-suppressing medication for 4-8 weeks is reasonable. A PPI is preferred to a histamine-2 receptor blocker. PPI safety studies are lacking, but case studies suggest an increase in infections in children taking acid-suppressing medications. Therefore, as with infants, if medications are used they should be prescribed at the lowest dose and for the shortest period of time possible. If medications are not helping, or need to be used long term, referral to a pediatric gastroenterologist can be considered. Of note, the guidelines do support a 4-8 week trial of PPIs in older children as a diagnostic test; this differs from the recommendations for infants, in whom a trial for diagnostic purposes is discouraged.
 

Diagnostic testing

Refer to a gastroenterologist for endoscopy in cases of persistent symptoms despite PPI use or failure to wean off medication. If there are no erosions, pH monitoring with pH-impedance monitoring or pH-metry can help distinguish between nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. If it is performed when a child is off of PPIs, endoscopy can also diagnose PPI-responsive eosinophilic esophagitis. Barium contrast, abdominal ultrasonography, and manometry may be considered during the course of a search for an alternative diagnosis, but they should not be used to diagnose or confirm GERD.

The bottom line

Most GER is physiologic and does not need treatment. First-line treatment for GERD in infants and children is nonpharmacologic intervention.
 

Reference

Rosen R et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):516-554.

Dr. Oh is a third year resident in the Family Medicine Residency at Abington-Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Gastroesophageal reflux (GER) is common in infants and often presents a challenge to doctors who try to balance changing evidence with concerns about complications and parents’ concerns about their infant’s discomfort. In a 2018 guideline, the writing committee defined GER as reflux of stomach contents to the esophagus. GER is considered pathologic and, therefore, gastroesophageal reflux disease (GERD) when it is associated with troublesome symptoms and/or complications that can include esophagitis and aspiration.

Infants

GERD is difficult to diagnose in infants. The symptoms of GERD, such as crying after feeds, regurgitation, and irritability, occur commonly in all infants and in any individual infant may not be reflective of GERD. Regurgitation is common, frequent and normal in infants up to 6 months of age. A common challenge occurs when families request treatment for infants with irritability, back arching, and/or regurgitation who are otherwise doing well. In this group of infants it is important to recognize that neither testing nor therapy is indicated unless there is difficulty with feeding, growth, acquisition of milestones, or red flag signs.

In infants with recurrent regurgitation history, physical exam is usually sufficient to distinguish uncomplicated GER from GERD and other more worrisome diagnoses. Red flag symptoms raise the possibility of a different diagnosis. Red flag symptoms include weight loss; lethargy; excessive irritability/pain; onset of vomiting for more than 6 months or persisting past 12-18 months of age; rapidly increasing head circumference; persistent forceful, nocturnal, bloody, or bilious vomiting; abdominal distention; rectal bleeding; and chronic diarrhea. GERD that starts after 6 months of age or which persists after 12 months of age warrants further evaluation, often with referral to a pediatric gastroenterologist.

When GERD is suspected, the first therapeutic steps are to institute behavioral changes. Caregivers should avoid overfeeding and modify the feeding pattern to more frequent feedings consisting of less volume at each feed. The addition of thickeners to feeds does reduce regurgitation, although it may not affect other GERD signs and symptoms. Formula can be thickened with rice cereal, which tends to be an affordable choice that doesn’t clog nipples. Enzymes present in breast milk digest cereal thickeners, so breast milk can be thickened with xanthum gum (after 1 year of age) or carob bean–based products (after 42 weeks gestation).

If these modifications do not improve symptoms, the next step is to change the type of feeds. Some infants in whom GERD is suspected actually have cow’s milk protein allergy (CMPA), so a trial of cow’s milk elimination is warranted. A breastfeeding mother can eliminate all dairy from her diet including casein and whey. Caregivers can switch to an extensively hydrolyzed formula or an amino acid–based formula. The guideline do not recommend soy-based formulas because they are not available in Europe and because a significant percentage of infants with CMPA also develop allergy to soy, and they do not recommend rice hydrolysate formula because of a lack of evidence. Dairy can be reintroduced at a later point. While positional changes including elevating the head of the crib or placing the infant in the left lateral position can help decrease GERD, the American Academy of Pediatrics strongly discourages these positions because of safety concerns, so the guidelines do not recommend positional change.

If a 2-4 week trial of nonpharmacologic interventions fails, the next step is referral to a pediatric gastroenterologist. If a pediatric gastroenterologist is not available, a 4-8 week trial of acid suppressive medication may be given. No trial has shown utility of a trial of acid suppression as a diagnostic test for GERD. Medication should only be used in infants with strongly suspected GERD and, per the guidelines, “should not be used for the treatment of visible regurgitation in otherwise healthy infants.” Medications to treat GER do not have evidence of efficacy, and there is evidence of an increased risk of infection with use of acid suppression, including an increased risk of necrotizing enterocolitis, pneumonia, upper respiratory tract infections, sepsis, urinary tract infections, and Clostridium difficile. If used, proton-pump inhibitors are preferred over histamine-2 receptor blockers. Antacids and alginates are not recommended.
 

Older children

In children with heartburn or regurgitation without red flag symptoms, a trial of lifestyle changes and dietary education may be initiated. If a child is overweight, it is important to inform the patient and parents that excess body weight is associated with GERD. The head of the bed can be elevated along with left lateral positioning. The guidelines do not support any probiotics or herbal medicines.

If bothersome symptoms persist, a trial of acid-suppressing medication for 4-8 weeks is reasonable. A PPI is preferred to a histamine-2 receptor blocker. PPI safety studies are lacking, but case studies suggest an increase in infections in children taking acid-suppressing medications. Therefore, as with infants, if medications are used they should be prescribed at the lowest dose and for the shortest period of time possible. If medications are not helping, or need to be used long term, referral to a pediatric gastroenterologist can be considered. Of note, the guidelines do support a 4-8 week trial of PPIs in older children as a diagnostic test; this differs from the recommendations for infants, in whom a trial for diagnostic purposes is discouraged.
 

Diagnostic testing

Refer to a gastroenterologist for endoscopy in cases of persistent symptoms despite PPI use or failure to wean off medication. If there are no erosions, pH monitoring with pH-impedance monitoring or pH-metry can help distinguish between nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. If it is performed when a child is off of PPIs, endoscopy can also diagnose PPI-responsive eosinophilic esophagitis. Barium contrast, abdominal ultrasonography, and manometry may be considered during the course of a search for an alternative diagnosis, but they should not be used to diagnose or confirm GERD.

The bottom line

Most GER is physiologic and does not need treatment. First-line treatment for GERD in infants and children is nonpharmacologic intervention.
 

Reference

Rosen R et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):516-554.

Dr. Oh is a third year resident in the Family Medicine Residency at Abington-Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

[email protected]

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

[email protected]

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) should include risk assessment and clinician-patient discussion that varies by the level of risk involved, according to the 2018 update to U.S. guidelines for cholesterol management from the American Heart Association and the American College of Cardiology.

The guideline also emphasizes “careful adherence to lifestyle recommendations at an early age [to] reduce risk factor burden over the lifespan and decrease the need for preventive drug therapies later in life,” Scott M. Grundy, MD, PhD, and Neil J. Stone, MD, said in a synopsis of the document in the Annals of Internal Medicine.

For primary prevention in patients aged 40-75 years, estimation of 10-year ASCVD risk – introduced in the 2013 guidelines – and stratification into one of four categories should set the stage for clinician-patient discussion. A score of less than 5% indicates low risk and should prompt a risk discussion that emphasizes lifestyle recommendations. “Statins are clinically efficacious in the latter three categories, but the higher the risk, the stronger the statin indication,” said Dr. Grundy of the University of Texas, Dallas, and Dr. Stone of Northwestern University, Chicago.


When risk status is uncertain, measurement of coronary artery calcium should be considered in patients aged 40-75 years with LDL cholesterol levels of 70-189 mg/dL who do no not have diabetes, they noted.

The guideline emphasizes secondary prevention with “maximally tolerated doses of statins” and the use of nonstatin drugs such as ezetimibe and PCSK9 inhibitors for patients with very high ASCVD risk – defined as a history of multiple major events or one event and other high-risk conditions, Dr. Grundy and Dr. Stone wrote.

Financial support for the Guideline Writing Committee for the 2018 Cholesterol Guidelines came from the AHA and the ACC. Dr. Grundy and Dr. Stone said that they had no relevant conflicts of interest.

[email protected]

SOURCE: Grundy SM and Stone NJ. Ann Intern Med. 2019 May 28. doi: 10.7326/M19-0365.

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]

TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.

Bruce Jancin/MDedge News

Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.

A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.

The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.

The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.

“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.

For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.

Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.

Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.

The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.

[email protected]