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CAROLINA findings reaffirm linagliptin’s safety, free glimepiride of CV-risk stigma
SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.
Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.
“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.
In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.
The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.
]And that’s what the CAROLINA findings delivered – a resolution to the “decades-long debate” about cardiovascular safety with glimepiride and likely other modern sulfonylureas, according to coinvestigator and cardiologist Nikolaus Marx, MD, a professor of medicine at Aachen (Germany) University.
The CAROLINA investigators randomized 1:1 more than 6,000 patients with type 2 diabetes at 607 sites in 43 countries to receive either linagliptin 5 mg daily or glimepiride 1-4 mg daily on a background therapy, in most cases, of metformin. The median diabetes duration was 6.3 years, and baseline hemoglobin A1c was 7.15%. In all, 42% of the patients had established cardiovascular disease, and 37% had two or more risk factors that were managed by standard care.
After a median follow-up of 6.3 years, there was no difference between linagliptin and glimepiride in the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (11.8% and 12%, respectively; P = .76), nor were there any differences in the individual components. Likewise, there were no differences between the two drugs in hospitalization for heart failure (3.7% and 3.1%, P = .18) or all-cause mortality (10.2% and 11.2%; P = .23), and no difference in glucose control – a drop of about 0.3% in the HbA1c level at 1 year, then a slow creep back to baseline at around 4 years.
“We believe cardiovascular safety should no longer be a consideration in [deciding] between these two agents,” said Dr. Rosenstock, who cochaired the session with Dr. Marx.
However, there was a modest weight gain with glimepiride, and a marked increase in the risk of moderate to severe hypoglycemia, compared with linagliptin (30.9% and 6.5%, respectively; P less than .0001). Both weight gain and hypoglycemia are recognized side effects of sulfonylureas.
Sulfonylureas are far less expensive than the DPP-4 inhibitors are, so “other than cost consideration ... [the findings] support use of DPP-4 inhibitors before sulfonylureas if hypoglycemia and weight gain are also considerations,” Dr. Rosenstock said.
Robert H. Eckel, MD, an endocrinologist, said he has been “taking people off sulfonylureas for years because I [wasn’t] sure they were safe. This study has helped me know that I can continue [them] safely.”
However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.
The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.
Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.
SOURCE: Rosenstock J et al. ADA 2019.
SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.
Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.
“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.
In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.
The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.
]And that’s what the CAROLINA findings delivered – a resolution to the “decades-long debate” about cardiovascular safety with glimepiride and likely other modern sulfonylureas, according to coinvestigator and cardiologist Nikolaus Marx, MD, a professor of medicine at Aachen (Germany) University.
The CAROLINA investigators randomized 1:1 more than 6,000 patients with type 2 diabetes at 607 sites in 43 countries to receive either linagliptin 5 mg daily or glimepiride 1-4 mg daily on a background therapy, in most cases, of metformin. The median diabetes duration was 6.3 years, and baseline hemoglobin A1c was 7.15%. In all, 42% of the patients had established cardiovascular disease, and 37% had two or more risk factors that were managed by standard care.
After a median follow-up of 6.3 years, there was no difference between linagliptin and glimepiride in the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (11.8% and 12%, respectively; P = .76), nor were there any differences in the individual components. Likewise, there were no differences between the two drugs in hospitalization for heart failure (3.7% and 3.1%, P = .18) or all-cause mortality (10.2% and 11.2%; P = .23), and no difference in glucose control – a drop of about 0.3% in the HbA1c level at 1 year, then a slow creep back to baseline at around 4 years.
“We believe cardiovascular safety should no longer be a consideration in [deciding] between these two agents,” said Dr. Rosenstock, who cochaired the session with Dr. Marx.
However, there was a modest weight gain with glimepiride, and a marked increase in the risk of moderate to severe hypoglycemia, compared with linagliptin (30.9% and 6.5%, respectively; P less than .0001). Both weight gain and hypoglycemia are recognized side effects of sulfonylureas.
Sulfonylureas are far less expensive than the DPP-4 inhibitors are, so “other than cost consideration ... [the findings] support use of DPP-4 inhibitors before sulfonylureas if hypoglycemia and weight gain are also considerations,” Dr. Rosenstock said.
Robert H. Eckel, MD, an endocrinologist, said he has been “taking people off sulfonylureas for years because I [wasn’t] sure they were safe. This study has helped me know that I can continue [them] safely.”
However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.
The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.
Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.
SOURCE: Rosenstock J et al. ADA 2019.
SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.
Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.
“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.
In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.
The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.
]And that’s what the CAROLINA findings delivered – a resolution to the “decades-long debate” about cardiovascular safety with glimepiride and likely other modern sulfonylureas, according to coinvestigator and cardiologist Nikolaus Marx, MD, a professor of medicine at Aachen (Germany) University.
The CAROLINA investigators randomized 1:1 more than 6,000 patients with type 2 diabetes at 607 sites in 43 countries to receive either linagliptin 5 mg daily or glimepiride 1-4 mg daily on a background therapy, in most cases, of metformin. The median diabetes duration was 6.3 years, and baseline hemoglobin A1c was 7.15%. In all, 42% of the patients had established cardiovascular disease, and 37% had two or more risk factors that were managed by standard care.
After a median follow-up of 6.3 years, there was no difference between linagliptin and glimepiride in the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (11.8% and 12%, respectively; P = .76), nor were there any differences in the individual components. Likewise, there were no differences between the two drugs in hospitalization for heart failure (3.7% and 3.1%, P = .18) or all-cause mortality (10.2% and 11.2%; P = .23), and no difference in glucose control – a drop of about 0.3% in the HbA1c level at 1 year, then a slow creep back to baseline at around 4 years.
“We believe cardiovascular safety should no longer be a consideration in [deciding] between these two agents,” said Dr. Rosenstock, who cochaired the session with Dr. Marx.
However, there was a modest weight gain with glimepiride, and a marked increase in the risk of moderate to severe hypoglycemia, compared with linagliptin (30.9% and 6.5%, respectively; P less than .0001). Both weight gain and hypoglycemia are recognized side effects of sulfonylureas.
Sulfonylureas are far less expensive than the DPP-4 inhibitors are, so “other than cost consideration ... [the findings] support use of DPP-4 inhibitors before sulfonylureas if hypoglycemia and weight gain are also considerations,” Dr. Rosenstock said.
Robert H. Eckel, MD, an endocrinologist, said he has been “taking people off sulfonylureas for years because I [wasn’t] sure they were safe. This study has helped me know that I can continue [them] safely.”
However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.
The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.
Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.
SOURCE: Rosenstock J et al. ADA 2019.
REPORTING FROM ADA 2019
EULAR keeps csDMARDs as top PsA drugs
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.
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.
“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.
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.
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.
“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.
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.
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.
“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.
REPORTING FROM EULAR 2019 CONGRESS
Could some elderly skip statins based on negative risk markers?
Older individuals with certain negative risk markers have a very low risk of atherosclerotic cardiovascular disease, raising the possibility that some could forgo preventive treatment even if it’s indicated by current standards of risk assessment.
Low levels of coronary artery calcification (CAC), low galectin-3 levels, and absence of carotid plaque were all linked to a lower likelihood of disease than might be expected based on traditional risk assessment, according to the authors of analysis of a large, contemporary cohort of elderly individuals published in the Journal of the American College of Cardiology.
“Our results hold the potential to markedly improve statin allocation in elderly individuals by de-escalating or even withholding preventive therapy in elderly individuals at truly low atherosclerotic cardiovascular disease risk despite advancing age,“ wrote Martin Bødtker Mortensen, MD, PhD, of Aarhus (Denmark) University Hospital.
Most elderly individuals now qualify for lifelong preventive statin treatment, based on the broader indication for treatment in recent guidelines, and the substantial impact that age has when risk is being calculated, Dr. Mortensen and coauthors said in their report.
“Because frailty, comorbidity, and polypharmacy are increasing concerns in elderly individuals and have been proposed to increase the risk for adverse effects, the appropriateness of treating almost all elderly individuals is questionable,” they said in the report.
In their study, Dr. Mortensen and colleagues evaluated a set of 13 biomarkers or imaging tests that they though had potential to “downgrade” risk of coronary heart disease (CHD) and cardiovascular disease (CVD). They based their analysis on 5,805 patients in the BioImage Study, a prospective cohort study of elderly men and women with no atherosclerotic cardiovascular disease at the time of enrollment in 2008 and 2009. The mean age at the time of enrollment was 69 years, and the mean follow-up in this analysis was 2.7 years.
The overall rate of CHD was 6.1 per 1,000 person-years, though looking at negative risk markers, the event rate was just 0.9 for individuals with CAC of 0 and also 0.9 for those with a CAC of 10 or less, followed by 1.7 for absence of carotid plaque, and 2.6 for galectin-3 in the bottom 25th percentile, according to Dr. Mortensen and coinvestigators. Similarly, the rate of CVD was 9.2 per 1,000 person-years overall, and just 3.2 for a CAC of 0, 2.8 for a CAC of 10 or lower, 4.4 for no carotid plaque, and 4.0 for low galectin-3.
Results were less impressive for other negative risk markers, including normal ankle-brachial index (ABI) test, lack of family history, and low levels of circulating biomarkers such as high-sensitivity C-reactive protein and lipoprotein (a).
Investigators also calculated diagnostic likelihood ratios (DLR), a measure they said assesses the value of performing a diagnostic test, with values lower than 1 indicating a specific marker has value for downgrading risk.
Zero or low CAC exerted the greatest downward change in pre- to post-test risk, according to the investigators, with a multivariable-adjusted DLR of 0.20 for CHD, translating into an 80% relative risk reduction. Similarly, the adjusted DLRs for zero or low CAC for CVD were 0.48 and 0.41, respectively, translating into a 59% risk reduction.
Low galectin-3 also resulted in significant downward change in that pre- to post-test risk, investigators added.
The BioImage Study was funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Dr. Mortensen had no disclosures related to the present analysis. Coauthors provided disclosures related to G3 Pharmaceuticals, Abbott Laboratories, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard, among others.
SOURCE: Mortensen MB et al. J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.04.049.
This study suggests that atherosclerosis imaging tests are the strongest negative risk factors identified to date in cardiovascular medicine. The results are clinically actionable and should shape our approach to these tests in clinical practice.
Atherosclerosis imaging tests could be important in preventing overuse of pharmacotherapy for primary prevention in older adults, nearly all of whom would be considered at elevated risk by current standards.
Results for other candidate markers in the study were generally unimpressive, though the finding that low galectin-3 levels predicted low cardiovascular risk is novel, highly interesting, and deserving of further study.
Meanwhile, guidelines are already taking notice of an emerging consensus on the value of imaging studies as a negative risk factor.
The 2018 prevention guidelines from the American College of Cardiology/American Heart Association recommend coronary artery calcium (CAC) testing to guide individualized patient decision-making in certain adults between the ages of 40 and 75 years who are at borderline to intermediate risk, and that using CAC results to reclassify risk is reasonable in those aged 76-80 years, they said.
For the first time, the ACC/AHA guidelines devoted a section to negative risk factors, specifically highlighting the value of CAC = 0 and stating that intensive statin therapy is of less value in such patients and can potentially be avoided.
Likewise, 2017 guidelines from the Society of Cardiovascular Computed Tomography say that aspirin for primary prevention can almost always be forgone in patients with a CAC of 0.
“The bar for preventive therapy has justifiably fallen, reaching a point where many patients will qualify based on their age alone,” the authors said.
In light of that development, negative risk factors might meaningfully downgrade risk and help identify individuals who can safely focus on lifestyle therapies and defer preventive medication.
Michael J. Blaha, MD, MPH, and Khurram Nasir, MD, MPH are with the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore; Dr. Nasir also is affiliated with the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn. Ron Blankstein, MD, is with the cardiovascular division, department of medicine, Brigham and Women’s Hospital, Boston. These comments are adapted from their editorial (J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.05.032 ). Dr. Blankstein reported research funding/grant support from Amgen and Astellas; Dr. Blaha and Dr. Nasir said they had no disclosures to report.
This study suggests that atherosclerosis imaging tests are the strongest negative risk factors identified to date in cardiovascular medicine. The results are clinically actionable and should shape our approach to these tests in clinical practice.
Atherosclerosis imaging tests could be important in preventing overuse of pharmacotherapy for primary prevention in older adults, nearly all of whom would be considered at elevated risk by current standards.
Results for other candidate markers in the study were generally unimpressive, though the finding that low galectin-3 levels predicted low cardiovascular risk is novel, highly interesting, and deserving of further study.
Meanwhile, guidelines are already taking notice of an emerging consensus on the value of imaging studies as a negative risk factor.
The 2018 prevention guidelines from the American College of Cardiology/American Heart Association recommend coronary artery calcium (CAC) testing to guide individualized patient decision-making in certain adults between the ages of 40 and 75 years who are at borderline to intermediate risk, and that using CAC results to reclassify risk is reasonable in those aged 76-80 years, they said.
For the first time, the ACC/AHA guidelines devoted a section to negative risk factors, specifically highlighting the value of CAC = 0 and stating that intensive statin therapy is of less value in such patients and can potentially be avoided.
Likewise, 2017 guidelines from the Society of Cardiovascular Computed Tomography say that aspirin for primary prevention can almost always be forgone in patients with a CAC of 0.
“The bar for preventive therapy has justifiably fallen, reaching a point where many patients will qualify based on their age alone,” the authors said.
In light of that development, negative risk factors might meaningfully downgrade risk and help identify individuals who can safely focus on lifestyle therapies and defer preventive medication.
Michael J. Blaha, MD, MPH, and Khurram Nasir, MD, MPH are with the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore; Dr. Nasir also is affiliated with the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn. Ron Blankstein, MD, is with the cardiovascular division, department of medicine, Brigham and Women’s Hospital, Boston. These comments are adapted from their editorial (J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.05.032 ). Dr. Blankstein reported research funding/grant support from Amgen and Astellas; Dr. Blaha and Dr. Nasir said they had no disclosures to report.
This study suggests that atherosclerosis imaging tests are the strongest negative risk factors identified to date in cardiovascular medicine. The results are clinically actionable and should shape our approach to these tests in clinical practice.
Atherosclerosis imaging tests could be important in preventing overuse of pharmacotherapy for primary prevention in older adults, nearly all of whom would be considered at elevated risk by current standards.
Results for other candidate markers in the study were generally unimpressive, though the finding that low galectin-3 levels predicted low cardiovascular risk is novel, highly interesting, and deserving of further study.
Meanwhile, guidelines are already taking notice of an emerging consensus on the value of imaging studies as a negative risk factor.
The 2018 prevention guidelines from the American College of Cardiology/American Heart Association recommend coronary artery calcium (CAC) testing to guide individualized patient decision-making in certain adults between the ages of 40 and 75 years who are at borderline to intermediate risk, and that using CAC results to reclassify risk is reasonable in those aged 76-80 years, they said.
For the first time, the ACC/AHA guidelines devoted a section to negative risk factors, specifically highlighting the value of CAC = 0 and stating that intensive statin therapy is of less value in such patients and can potentially be avoided.
Likewise, 2017 guidelines from the Society of Cardiovascular Computed Tomography say that aspirin for primary prevention can almost always be forgone in patients with a CAC of 0.
“The bar for preventive therapy has justifiably fallen, reaching a point where many patients will qualify based on their age alone,” the authors said.
In light of that development, negative risk factors might meaningfully downgrade risk and help identify individuals who can safely focus on lifestyle therapies and defer preventive medication.
Michael J. Blaha, MD, MPH, and Khurram Nasir, MD, MPH are with the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore; Dr. Nasir also is affiliated with the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn. Ron Blankstein, MD, is with the cardiovascular division, department of medicine, Brigham and Women’s Hospital, Boston. These comments are adapted from their editorial (J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.05.032 ). Dr. Blankstein reported research funding/grant support from Amgen and Astellas; Dr. Blaha and Dr. Nasir said they had no disclosures to report.
Older individuals with certain negative risk markers have a very low risk of atherosclerotic cardiovascular disease, raising the possibility that some could forgo preventive treatment even if it’s indicated by current standards of risk assessment.
Low levels of coronary artery calcification (CAC), low galectin-3 levels, and absence of carotid plaque were all linked to a lower likelihood of disease than might be expected based on traditional risk assessment, according to the authors of analysis of a large, contemporary cohort of elderly individuals published in the Journal of the American College of Cardiology.
“Our results hold the potential to markedly improve statin allocation in elderly individuals by de-escalating or even withholding preventive therapy in elderly individuals at truly low atherosclerotic cardiovascular disease risk despite advancing age,“ wrote Martin Bødtker Mortensen, MD, PhD, of Aarhus (Denmark) University Hospital.
Most elderly individuals now qualify for lifelong preventive statin treatment, based on the broader indication for treatment in recent guidelines, and the substantial impact that age has when risk is being calculated, Dr. Mortensen and coauthors said in their report.
“Because frailty, comorbidity, and polypharmacy are increasing concerns in elderly individuals and have been proposed to increase the risk for adverse effects, the appropriateness of treating almost all elderly individuals is questionable,” they said in the report.
In their study, Dr. Mortensen and colleagues evaluated a set of 13 biomarkers or imaging tests that they though had potential to “downgrade” risk of coronary heart disease (CHD) and cardiovascular disease (CVD). They based their analysis on 5,805 patients in the BioImage Study, a prospective cohort study of elderly men and women with no atherosclerotic cardiovascular disease at the time of enrollment in 2008 and 2009. The mean age at the time of enrollment was 69 years, and the mean follow-up in this analysis was 2.7 years.
The overall rate of CHD was 6.1 per 1,000 person-years, though looking at negative risk markers, the event rate was just 0.9 for individuals with CAC of 0 and also 0.9 for those with a CAC of 10 or less, followed by 1.7 for absence of carotid plaque, and 2.6 for galectin-3 in the bottom 25th percentile, according to Dr. Mortensen and coinvestigators. Similarly, the rate of CVD was 9.2 per 1,000 person-years overall, and just 3.2 for a CAC of 0, 2.8 for a CAC of 10 or lower, 4.4 for no carotid plaque, and 4.0 for low galectin-3.
Results were less impressive for other negative risk markers, including normal ankle-brachial index (ABI) test, lack of family history, and low levels of circulating biomarkers such as high-sensitivity C-reactive protein and lipoprotein (a).
Investigators also calculated diagnostic likelihood ratios (DLR), a measure they said assesses the value of performing a diagnostic test, with values lower than 1 indicating a specific marker has value for downgrading risk.
Zero or low CAC exerted the greatest downward change in pre- to post-test risk, according to the investigators, with a multivariable-adjusted DLR of 0.20 for CHD, translating into an 80% relative risk reduction. Similarly, the adjusted DLRs for zero or low CAC for CVD were 0.48 and 0.41, respectively, translating into a 59% risk reduction.
Low galectin-3 also resulted in significant downward change in that pre- to post-test risk, investigators added.
The BioImage Study was funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Dr. Mortensen had no disclosures related to the present analysis. Coauthors provided disclosures related to G3 Pharmaceuticals, Abbott Laboratories, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard, among others.
SOURCE: Mortensen MB et al. J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.04.049.
Older individuals with certain negative risk markers have a very low risk of atherosclerotic cardiovascular disease, raising the possibility that some could forgo preventive treatment even if it’s indicated by current standards of risk assessment.
Low levels of coronary artery calcification (CAC), low galectin-3 levels, and absence of carotid plaque were all linked to a lower likelihood of disease than might be expected based on traditional risk assessment, according to the authors of analysis of a large, contemporary cohort of elderly individuals published in the Journal of the American College of Cardiology.
“Our results hold the potential to markedly improve statin allocation in elderly individuals by de-escalating or even withholding preventive therapy in elderly individuals at truly low atherosclerotic cardiovascular disease risk despite advancing age,“ wrote Martin Bødtker Mortensen, MD, PhD, of Aarhus (Denmark) University Hospital.
Most elderly individuals now qualify for lifelong preventive statin treatment, based on the broader indication for treatment in recent guidelines, and the substantial impact that age has when risk is being calculated, Dr. Mortensen and coauthors said in their report.
“Because frailty, comorbidity, and polypharmacy are increasing concerns in elderly individuals and have been proposed to increase the risk for adverse effects, the appropriateness of treating almost all elderly individuals is questionable,” they said in the report.
In their study, Dr. Mortensen and colleagues evaluated a set of 13 biomarkers or imaging tests that they though had potential to “downgrade” risk of coronary heart disease (CHD) and cardiovascular disease (CVD). They based their analysis on 5,805 patients in the BioImage Study, a prospective cohort study of elderly men and women with no atherosclerotic cardiovascular disease at the time of enrollment in 2008 and 2009. The mean age at the time of enrollment was 69 years, and the mean follow-up in this analysis was 2.7 years.
The overall rate of CHD was 6.1 per 1,000 person-years, though looking at negative risk markers, the event rate was just 0.9 for individuals with CAC of 0 and also 0.9 for those with a CAC of 10 or less, followed by 1.7 for absence of carotid plaque, and 2.6 for galectin-3 in the bottom 25th percentile, according to Dr. Mortensen and coinvestigators. Similarly, the rate of CVD was 9.2 per 1,000 person-years overall, and just 3.2 for a CAC of 0, 2.8 for a CAC of 10 or lower, 4.4 for no carotid plaque, and 4.0 for low galectin-3.
Results were less impressive for other negative risk markers, including normal ankle-brachial index (ABI) test, lack of family history, and low levels of circulating biomarkers such as high-sensitivity C-reactive protein and lipoprotein (a).
Investigators also calculated diagnostic likelihood ratios (DLR), a measure they said assesses the value of performing a diagnostic test, with values lower than 1 indicating a specific marker has value for downgrading risk.
Zero or low CAC exerted the greatest downward change in pre- to post-test risk, according to the investigators, with a multivariable-adjusted DLR of 0.20 for CHD, translating into an 80% relative risk reduction. Similarly, the adjusted DLRs for zero or low CAC for CVD were 0.48 and 0.41, respectively, translating into a 59% risk reduction.
Low galectin-3 also resulted in significant downward change in that pre- to post-test risk, investigators added.
The BioImage Study was funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Dr. Mortensen had no disclosures related to the present analysis. Coauthors provided disclosures related to G3 Pharmaceuticals, Abbott Laboratories, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard, among others.
SOURCE: Mortensen MB et al. J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.04.049.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Low or no coronary artery calcification (CAC), low galectin-3 levels, and absence of carotid plaque were all linked to a lower likelihood of atherosclerotic cardiovascular disease in elderly patients, suggesting pharmacotherapy might be avoidable in a certain proportion of them.
Major finding: The diagnostic likelihood ratios (DLR) were low for those negative risk markers, e.g., 0.20 for no or low CAC, indicating a relative risk reduction of about 80%.
Study details: Analysis of data from the BioImage Study, a prospective cohort study of 5,805 older men and women who had no atherosclerotic cardiovascular disease at the time of enrollment.
Disclosures: The BioImage Study was funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Authors of the present analysis provided disclosures related to G3 Pharmaceuticals, Abbott Laboratories, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard, among others.
Source: Mortensen MB et al. J Am Coll Cardiol. 2019 Jul 1. doi: j.jacc.2019.04.049.
Lipoprotein(a) levels tied to higher ischemic stroke risk
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
This study linking high lipoprotein(a) [Lp(a)] levels to stroke risk, taken together with previous research, provide a sound basis to routinely perform one-time screening so that individuals with inherited high levels can try to avoid adverse cardiovascular outcomes, according to Christie M. Ballantyne, MD.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of myocardial infarction, stroke, and aortic valve stenosis,” Dr. Ballantyne wrote in an editorial comment on the study.
Evidence is now “overwhelming” that high Lp(a) is linked to myocardial infarction and stroke, and it’s known that statins and aspirin reduce risk of these outcomes, he said in the commentary.
Despite that, scientific statements do not recommend routine Lp(a) testing due to a lack of clinical trials evidence; as a result, clinical trials are not including Lp(a) as a routine measurement: “We thus have a loop of futility—lack of routine measurement leads to lack of data,” he said.
This most recent study from Langsted and colleagues demonstrates that high Lp(a) levels, and genetic variants associated with Lp(a), are associated with increased ischemic stroke risk. “The genetics strongly supported that high Lp(a) levels were in the causal pathway for ischemic stroke and coronary heart disease,” Dr. Ballantyne said.
One major strength and weakness of the study is its large and relatively homogeneous European population—that bolstered the genetic analyses, but also means the data can’t be extrapolated to other populations, such as Africans and East Asians, who have higher stroke rates compared with Europeans, Dr. Ballantyne said.
Dr. Ballantyne is with the Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Tex. His editorial comment appears in the Journal of the American College of Cardiology (2019;74[1]:67-9. doi:10.1016/j.jacc.2019.05.029 . Dr. Ballantyne reported disclosures related to Akcea, Amgen, and Novartis.
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.
Anne Langsted, MD, with Copenhagen University Hospital and the University of Copenhagen in Denmark, and her co-researchers evaluated the impact of high Lp(a) levels in a large contemporary cohort of 49,699 individuals in the Copenhagen General Population Study, and another 10,813 individuals in the Copenhagen City Heart Study.
Measurements assessed included plasma lipoprotein(a) levels and carrier or noncarrier status for LPA rs10455872. The endpoint of ischemic stroke was ascertained from Danish national health registries and confirmed by physicians.
Although risk estimates were less pronounced than what was reported before regarding the link between Lp(a) for ischemic heart disease and aortic valve stenosis, the risk of stroke was increased by a factor of 1.6 among individuals with high Lp(a) levels as compared to those with lower levels, the investigators said.
Compared with noncarriers of LPA rs1045572, the hazard ratio for ischemic stroke was 1.23 for carriers of LPA rs1045572, which was associated with high levels plasma lipoprotein(a) levels, according to the researchers.
“Our results indicate a causal association of Lp(a) with risk of ischemic stroke, and emphasize the need for randomized, controlled clinical trials on the effect of Lp(a)-lowering to prevent cardiovascular disease including ischemic stroke,” About 20% of the general population have high Lp(a) levels, and some individuals have extremely high levels, Dr. Langsted and co-authors said in their report.
Interest in Lp(a) as a risk factor for cardiovascular disease has been reignited following large studies showing that high Lp(a) levels were linked to increased risk of myocardial infarction and aortic valve stenosis, according to the investigators.
However, results of various studies are conflicting as to whether high Lp(a) levels increase risk of hemorrhagic or ischemic stroke, they said.
Both cohort studies used in the analysis were supported by sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures. One co-author reported disclosures related to Akcea, Amgen, Sanofi, Regeneron, and AstraZeneca.
SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: Stroke risk was 1.6X higher with high Lp(a) levels.
Study details: Analysis of 49,699 individuals in the Copenhagen General Population Study, and 10,813 individuals in the Copenhagen City Heart Study.
Disclosures: Both studies were supported by the sources in Denmark including the Danish Medical Research Council and Copenhagen University Hospital. Dr. Langsted had no disclosures.
Source: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524
Data sharing to third parties prevalent in depression, smoking cessation apps
“Mechanisms that potentially enable a small number of dominant online service providers to link information about the use of mental health apps, without either user consent or awareness, appear to be prevalent,” Kit Huckvale, MB ChB, MSc, PhD, of Black Dog Institute at the University of New South Wales Sydney in Randwick, New South Wales, Australia, and colleagues wrote in their study. “Mismatches between declared privacy policies and observed behavior highlight the continuing need for innovation around trust and transparency for health apps.” The study was published in JAMA Network Open.
Dr. Huckvale and colleagues examined the top 36 depression and smoking cessation apps for Android and iOS in the United States accessed in January 2018; Of the apps downloaded, 15 apps were Android-only, 14 apps were iOS-only, and 7 apps were available on both platforms. The apps were assessed over a series of two sessions while network traffic was captured during use, which allowed researchers to determine what personal information was in each data transmission and where the information was going.
There were 25 apps with a privacy policy (69%), 22 of 25 apps (88%) described how that app primarily collected data, and only 16 of 25 apps (64%) provided information on secondary uses of data. Despite 23 of 25 apps (92%) addressing “the possibility of transmission of data to any third party,” 33 of 36 apps overall (92%) transmitted data to third parties. The two most common entities that received third-party data for marketing, advertising, or analytic purposes were Google and Facebook (29 of 36 apps; 81%). However, 12 of 28 apps (43%) that sent data to Google and 6 of 12 apps (50%) that sent data to Facebook disclosed that they would share data with those companies.
The type of data sent to Google and Facebook consisted of a strong identifier to the device or a username (9 of 33 apps; 27%), or a weak identifier in the form of an advertising identifier or a pseudonymous profile that can link users to their behavior on the app and on other products and platforms (26 of 33 apps; 79%).
“As smartphones continue to gain capabilities to collect new forms of personal, biometric, and health information, it is imperative for the health care community to respond with new methods and processes to review apps and ensure they remain safe and protect personal health information,” the researchers concluded.
One of the investigators, Mark E. Larsen, DPhil, reported receiving grants from National Health and Medical Research Council. The other authors reported no relevant conflicts of interest.
SOURCE: Huckvale K et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.2542.
“Mechanisms that potentially enable a small number of dominant online service providers to link information about the use of mental health apps, without either user consent or awareness, appear to be prevalent,” Kit Huckvale, MB ChB, MSc, PhD, of Black Dog Institute at the University of New South Wales Sydney in Randwick, New South Wales, Australia, and colleagues wrote in their study. “Mismatches between declared privacy policies and observed behavior highlight the continuing need for innovation around trust and transparency for health apps.” The study was published in JAMA Network Open.
Dr. Huckvale and colleagues examined the top 36 depression and smoking cessation apps for Android and iOS in the United States accessed in January 2018; Of the apps downloaded, 15 apps were Android-only, 14 apps were iOS-only, and 7 apps were available on both platforms. The apps were assessed over a series of two sessions while network traffic was captured during use, which allowed researchers to determine what personal information was in each data transmission and where the information was going.
There were 25 apps with a privacy policy (69%), 22 of 25 apps (88%) described how that app primarily collected data, and only 16 of 25 apps (64%) provided information on secondary uses of data. Despite 23 of 25 apps (92%) addressing “the possibility of transmission of data to any third party,” 33 of 36 apps overall (92%) transmitted data to third parties. The two most common entities that received third-party data for marketing, advertising, or analytic purposes were Google and Facebook (29 of 36 apps; 81%). However, 12 of 28 apps (43%) that sent data to Google and 6 of 12 apps (50%) that sent data to Facebook disclosed that they would share data with those companies.
The type of data sent to Google and Facebook consisted of a strong identifier to the device or a username (9 of 33 apps; 27%), or a weak identifier in the form of an advertising identifier or a pseudonymous profile that can link users to their behavior on the app and on other products and platforms (26 of 33 apps; 79%).
“As smartphones continue to gain capabilities to collect new forms of personal, biometric, and health information, it is imperative for the health care community to respond with new methods and processes to review apps and ensure they remain safe and protect personal health information,” the researchers concluded.
One of the investigators, Mark E. Larsen, DPhil, reported receiving grants from National Health and Medical Research Council. The other authors reported no relevant conflicts of interest.
SOURCE: Huckvale K et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.2542.
“Mechanisms that potentially enable a small number of dominant online service providers to link information about the use of mental health apps, without either user consent or awareness, appear to be prevalent,” Kit Huckvale, MB ChB, MSc, PhD, of Black Dog Institute at the University of New South Wales Sydney in Randwick, New South Wales, Australia, and colleagues wrote in their study. “Mismatches between declared privacy policies and observed behavior highlight the continuing need for innovation around trust and transparency for health apps.” The study was published in JAMA Network Open.
Dr. Huckvale and colleagues examined the top 36 depression and smoking cessation apps for Android and iOS in the United States accessed in January 2018; Of the apps downloaded, 15 apps were Android-only, 14 apps were iOS-only, and 7 apps were available on both platforms. The apps were assessed over a series of two sessions while network traffic was captured during use, which allowed researchers to determine what personal information was in each data transmission and where the information was going.
There were 25 apps with a privacy policy (69%), 22 of 25 apps (88%) described how that app primarily collected data, and only 16 of 25 apps (64%) provided information on secondary uses of data. Despite 23 of 25 apps (92%) addressing “the possibility of transmission of data to any third party,” 33 of 36 apps overall (92%) transmitted data to third parties. The two most common entities that received third-party data for marketing, advertising, or analytic purposes were Google and Facebook (29 of 36 apps; 81%). However, 12 of 28 apps (43%) that sent data to Google and 6 of 12 apps (50%) that sent data to Facebook disclosed that they would share data with those companies.
The type of data sent to Google and Facebook consisted of a strong identifier to the device or a username (9 of 33 apps; 27%), or a weak identifier in the form of an advertising identifier or a pseudonymous profile that can link users to their behavior on the app and on other products and platforms (26 of 33 apps; 79%).
“As smartphones continue to gain capabilities to collect new forms of personal, biometric, and health information, it is imperative for the health care community to respond with new methods and processes to review apps and ensure they remain safe and protect personal health information,” the researchers concluded.
One of the investigators, Mark E. Larsen, DPhil, reported receiving grants from National Health and Medical Research Council. The other authors reported no relevant conflicts of interest.
SOURCE: Huckvale K et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.2542.
FROM JAMA NETWORK OPEN
More cognitive rigidity found in patients with depression plus fibromyalgia
Increasing cognitive complexity cited as a possible therapeutic target
More attention might need to be paid to the role of chronic pain in the treatment of patients with comorbid depression, researchers suggest.
“Maybe models of depression should differentiate between depressed patients with a chronic pain condition, such as [fibromyalgia], and those without pain, wrote Mari Aguilera of the department of cognition, development, and educational psychology at the University of Barcelona and associates.
The research involved 62 patients who had participated in a previous randomized controlled trial that had assessed the efficacy of a dilemma-focused intervention for depression. All patients in the trial had met the criteria for major depressive disorder and/or dysthymia and had a score of more than 19 on the Beck Depression Inventory-II (BDI-II) scale, the investigators reported in the International Journal of Clinical and Health Psychology.
For the current trial, the researchers studied 31 patients from the trial who had an average age of 50, a concurrent diagnosis of fibromyalgia for an average of 8.14 years, an average of 2.06 depressive episodes, and a mean pain intensity of 76.21 on the visual analog scale.
The matched group of 31 patients who were used as a comparator group did not have a diagnosis of fibromyalgia and did not report high levels of pain intensity. Results showed that, in line with the researchers’ expectations, depressed patients with fibromyalgia had significantly higher BDI-II scores than patients with depression alone.
The researchers noted that patients with comorbid fibromyalgia had higher scores in pessimism, irritability, concentration/difficulty, tiredness or fatigue, and loss of interest in sex, compared with the control group.
“The nature of the relationship between pain and depression needs further studies to develop a better understanding in the future,” they wrote. The study was published in the International Journal of Clinical and Health Psychology.
Patients with comorbid fibromyalgia had higher levels of depressive symptoms and greater cognitive rigidity than did controls, the researchers found. Those with comorbid depression and pain also displayed higher levels of polarization, compared with the matched patients, with a medium-sized effect.
The small study size was cited as a limitation for generalizability. However, if confirmed by other larger studies, the researchers said, the findings might have implications for the treatment of depressed patients with comorbid fibromyalgia. “For patients with chronic pain, increasing their cognitive complexity might lead to better therapeutic results,” they wrote. “Overall, our study points to the need for more attention to the role of chronic pain in the study and treatment of depressed patients.
The research was funded by Spain’s Ministry of Science and Innovation.
SOURCE: Aguilera M et al. Int J Clin Health Psychol. 2019 May;19(2):160-4.
Increasing cognitive complexity cited as a possible therapeutic target
Increasing cognitive complexity cited as a possible therapeutic target
More attention might need to be paid to the role of chronic pain in the treatment of patients with comorbid depression, researchers suggest.
“Maybe models of depression should differentiate between depressed patients with a chronic pain condition, such as [fibromyalgia], and those without pain, wrote Mari Aguilera of the department of cognition, development, and educational psychology at the University of Barcelona and associates.
The research involved 62 patients who had participated in a previous randomized controlled trial that had assessed the efficacy of a dilemma-focused intervention for depression. All patients in the trial had met the criteria for major depressive disorder and/or dysthymia and had a score of more than 19 on the Beck Depression Inventory-II (BDI-II) scale, the investigators reported in the International Journal of Clinical and Health Psychology.
For the current trial, the researchers studied 31 patients from the trial who had an average age of 50, a concurrent diagnosis of fibromyalgia for an average of 8.14 years, an average of 2.06 depressive episodes, and a mean pain intensity of 76.21 on the visual analog scale.
The matched group of 31 patients who were used as a comparator group did not have a diagnosis of fibromyalgia and did not report high levels of pain intensity. Results showed that, in line with the researchers’ expectations, depressed patients with fibromyalgia had significantly higher BDI-II scores than patients with depression alone.
The researchers noted that patients with comorbid fibromyalgia had higher scores in pessimism, irritability, concentration/difficulty, tiredness or fatigue, and loss of interest in sex, compared with the control group.
“The nature of the relationship between pain and depression needs further studies to develop a better understanding in the future,” they wrote. The study was published in the International Journal of Clinical and Health Psychology.
Patients with comorbid fibromyalgia had higher levels of depressive symptoms and greater cognitive rigidity than did controls, the researchers found. Those with comorbid depression and pain also displayed higher levels of polarization, compared with the matched patients, with a medium-sized effect.
The small study size was cited as a limitation for generalizability. However, if confirmed by other larger studies, the researchers said, the findings might have implications for the treatment of depressed patients with comorbid fibromyalgia. “For patients with chronic pain, increasing their cognitive complexity might lead to better therapeutic results,” they wrote. “Overall, our study points to the need for more attention to the role of chronic pain in the study and treatment of depressed patients.
The research was funded by Spain’s Ministry of Science and Innovation.
SOURCE: Aguilera M et al. Int J Clin Health Psychol. 2019 May;19(2):160-4.
More attention might need to be paid to the role of chronic pain in the treatment of patients with comorbid depression, researchers suggest.
“Maybe models of depression should differentiate between depressed patients with a chronic pain condition, such as [fibromyalgia], and those without pain, wrote Mari Aguilera of the department of cognition, development, and educational psychology at the University of Barcelona and associates.
The research involved 62 patients who had participated in a previous randomized controlled trial that had assessed the efficacy of a dilemma-focused intervention for depression. All patients in the trial had met the criteria for major depressive disorder and/or dysthymia and had a score of more than 19 on the Beck Depression Inventory-II (BDI-II) scale, the investigators reported in the International Journal of Clinical and Health Psychology.
For the current trial, the researchers studied 31 patients from the trial who had an average age of 50, a concurrent diagnosis of fibromyalgia for an average of 8.14 years, an average of 2.06 depressive episodes, and a mean pain intensity of 76.21 on the visual analog scale.
The matched group of 31 patients who were used as a comparator group did not have a diagnosis of fibromyalgia and did not report high levels of pain intensity. Results showed that, in line with the researchers’ expectations, depressed patients with fibromyalgia had significantly higher BDI-II scores than patients with depression alone.
The researchers noted that patients with comorbid fibromyalgia had higher scores in pessimism, irritability, concentration/difficulty, tiredness or fatigue, and loss of interest in sex, compared with the control group.
“The nature of the relationship between pain and depression needs further studies to develop a better understanding in the future,” they wrote. The study was published in the International Journal of Clinical and Health Psychology.
Patients with comorbid fibromyalgia had higher levels of depressive symptoms and greater cognitive rigidity than did controls, the researchers found. Those with comorbid depression and pain also displayed higher levels of polarization, compared with the matched patients, with a medium-sized effect.
The small study size was cited as a limitation for generalizability. However, if confirmed by other larger studies, the researchers said, the findings might have implications for the treatment of depressed patients with comorbid fibromyalgia. “For patients with chronic pain, increasing their cognitive complexity might lead to better therapeutic results,” they wrote. “Overall, our study points to the need for more attention to the role of chronic pain in the study and treatment of depressed patients.
The research was funded by Spain’s Ministry of Science and Innovation.
SOURCE: Aguilera M et al. Int J Clin Health Psychol. 2019 May;19(2):160-4.
FROM THE INTERNATIONAL JOURNAL OF CLINICAL AND HEALTH PSYCHOLOGY
Hyperthyroid? She sure doesn’t look like it
A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.
A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.
A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.
I don’t have much use for evidence
.
Of course I am not against evidence. I respect and value evidence. I just have little day-to-day use for it. Maybe your practices are different from mine, but I spend my working days seeing cases ...
Where evidence is irrelevant:
- there is nothing wrong but the patient thinks there might be (an itch, a burning sensation, a mole that may or may not have changed).
- the condition is self-limiting and needs no therapy (viral rashes).
Where evidence could help, but there isn’t any:
- there is no useful available treatment (age-related hair thinning in women).
Where evidence may be statistically significant but clinically trivial:
- pills that make herpes simplex cold sores go away in 6 days instead of 7, acne cream that reduces lesions by 70% instead of 40% (so that after 12 weeks the patient has five pimples instead of eight).
Where evidence is unimpressive or unconvincing (to the patient, who often stops treatment because “it wasn’t working” or “it made me worse”):
- the condition is recurrent, and the patient interprets recurrence as failure (eczema, psoriasis).
- the condition (psoriasis, eczema, acne ) moves around, and the patient interprets success (fewer spots) as failure. (“It’s come in a new place it never came before” or “I never used to get pimples on my jawline.”)
- slam-dunk clearances are few, and instead, every possible permutation in the condition’s course happens – persistence, recurrence, extension, spontaneous involution, going away in one place while proliferating in another, etc. (warts, alopecia areata).
Where patients find other kinds of evidence more compelling than mine:
- “I stopped your cream because calendula/tea tree oil/Vicks VapoRub/apple cider vinegar/avoiding gluten works better” (eczema, rosacea, onychomycosis, etc.). This dynamic is not limited to dermatology. How many Crohn’s patients have I met who say they left their conventional physicians with their standard treatments and now see a naturopath or acupuncturist? Their doctors don’t know they left, or why, because it’s impossible to remember someone who isn’t there, and their patients never told them why they left. These patients tell me they are now “doing better.”
Where evidence is outweighed by other patient considerations:
- topical 5-fluorouracil or imiquimod for superficial basal cells or noninvasive squamous cells in a patient who can’t reach the spot, doesn’t want to be bothered, or just wants the damned thing cut off.
Then, of course, there are cases where evidence is crucial. It’s just that, at the moment, I can’t think of many. Besides which, I’ve lost count of all the patients who had exhaustive food or patch testing, been found sensitive to any number of chemicals and foods – exotic or otherwise – dutifully avoided all of same, yet still break out intermittently and inscrutably, just like all my other atopics.
I’ve concluded that it must be me, or at least the small slice of the planet I work in. Maybe if I practice for 70 years instead of 40, or on five continents instead of the corner of just one, I will figure it all out.
To be clear: I am not a therapeutic nihilist. I want to use verifiably effective treatments for my patients, just as I wish such to be used on me when I need treatment. It’s just that instances in which compelling, decisive evidence makes a crucial difference don’t come up all that often. Evidence applies to populations, whereas I treat people, one at a time.
Meantime, I will muddle along, concerned that one drawback of the emphasis on “evidence” (i.e. statistics) not often noted is its contribution to depersonalizing medical practice, reducing the therapeutic interaction between two people to iterated instances of quantifiable throughput. If you can’t measure it, you didn’t do it and it doesn’t exist. But it does exist. Like every clinician, I see and do it every day.
As Hippocrates supposedly said: Life is short, and art long, opportunity fleeting, experimentations perilous, and judgment difficult.
Evidence notwithstanding, judgment remains difficult, mine and the patient’s.
Now that I’m done with evidence, please stay tuned for future columns where I take on motherhood (unacceptably gendered!) and apple pie (fattening!)
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
.
Of course I am not against evidence. I respect and value evidence. I just have little day-to-day use for it. Maybe your practices are different from mine, but I spend my working days seeing cases ...
Where evidence is irrelevant:
- there is nothing wrong but the patient thinks there might be (an itch, a burning sensation, a mole that may or may not have changed).
- the condition is self-limiting and needs no therapy (viral rashes).
Where evidence could help, but there isn’t any:
- there is no useful available treatment (age-related hair thinning in women).
Where evidence may be statistically significant but clinically trivial:
- pills that make herpes simplex cold sores go away in 6 days instead of 7, acne cream that reduces lesions by 70% instead of 40% (so that after 12 weeks the patient has five pimples instead of eight).
Where evidence is unimpressive or unconvincing (to the patient, who often stops treatment because “it wasn’t working” or “it made me worse”):
- the condition is recurrent, and the patient interprets recurrence as failure (eczema, psoriasis).
- the condition (psoriasis, eczema, acne ) moves around, and the patient interprets success (fewer spots) as failure. (“It’s come in a new place it never came before” or “I never used to get pimples on my jawline.”)
- slam-dunk clearances are few, and instead, every possible permutation in the condition’s course happens – persistence, recurrence, extension, spontaneous involution, going away in one place while proliferating in another, etc. (warts, alopecia areata).
Where patients find other kinds of evidence more compelling than mine:
- “I stopped your cream because calendula/tea tree oil/Vicks VapoRub/apple cider vinegar/avoiding gluten works better” (eczema, rosacea, onychomycosis, etc.). This dynamic is not limited to dermatology. How many Crohn’s patients have I met who say they left their conventional physicians with their standard treatments and now see a naturopath or acupuncturist? Their doctors don’t know they left, or why, because it’s impossible to remember someone who isn’t there, and their patients never told them why they left. These patients tell me they are now “doing better.”
Where evidence is outweighed by other patient considerations:
- topical 5-fluorouracil or imiquimod for superficial basal cells or noninvasive squamous cells in a patient who can’t reach the spot, doesn’t want to be bothered, or just wants the damned thing cut off.
Then, of course, there are cases where evidence is crucial. It’s just that, at the moment, I can’t think of many. Besides which, I’ve lost count of all the patients who had exhaustive food or patch testing, been found sensitive to any number of chemicals and foods – exotic or otherwise – dutifully avoided all of same, yet still break out intermittently and inscrutably, just like all my other atopics.
I’ve concluded that it must be me, or at least the small slice of the planet I work in. Maybe if I practice for 70 years instead of 40, or on five continents instead of the corner of just one, I will figure it all out.
To be clear: I am not a therapeutic nihilist. I want to use verifiably effective treatments for my patients, just as I wish such to be used on me when I need treatment. It’s just that instances in which compelling, decisive evidence makes a crucial difference don’t come up all that often. Evidence applies to populations, whereas I treat people, one at a time.
Meantime, I will muddle along, concerned that one drawback of the emphasis on “evidence” (i.e. statistics) not often noted is its contribution to depersonalizing medical practice, reducing the therapeutic interaction between two people to iterated instances of quantifiable throughput. If you can’t measure it, you didn’t do it and it doesn’t exist. But it does exist. Like every clinician, I see and do it every day.
As Hippocrates supposedly said: Life is short, and art long, opportunity fleeting, experimentations perilous, and judgment difficult.
Evidence notwithstanding, judgment remains difficult, mine and the patient’s.
Now that I’m done with evidence, please stay tuned for future columns where I take on motherhood (unacceptably gendered!) and apple pie (fattening!)
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
.
Of course I am not against evidence. I respect and value evidence. I just have little day-to-day use for it. Maybe your practices are different from mine, but I spend my working days seeing cases ...
Where evidence is irrelevant:
- there is nothing wrong but the patient thinks there might be (an itch, a burning sensation, a mole that may or may not have changed).
- the condition is self-limiting and needs no therapy (viral rashes).
Where evidence could help, but there isn’t any:
- there is no useful available treatment (age-related hair thinning in women).
Where evidence may be statistically significant but clinically trivial:
- pills that make herpes simplex cold sores go away in 6 days instead of 7, acne cream that reduces lesions by 70% instead of 40% (so that after 12 weeks the patient has five pimples instead of eight).
Where evidence is unimpressive or unconvincing (to the patient, who often stops treatment because “it wasn’t working” or “it made me worse”):
- the condition is recurrent, and the patient interprets recurrence as failure (eczema, psoriasis).
- the condition (psoriasis, eczema, acne ) moves around, and the patient interprets success (fewer spots) as failure. (“It’s come in a new place it never came before” or “I never used to get pimples on my jawline.”)
- slam-dunk clearances are few, and instead, every possible permutation in the condition’s course happens – persistence, recurrence, extension, spontaneous involution, going away in one place while proliferating in another, etc. (warts, alopecia areata).
Where patients find other kinds of evidence more compelling than mine:
- “I stopped your cream because calendula/tea tree oil/Vicks VapoRub/apple cider vinegar/avoiding gluten works better” (eczema, rosacea, onychomycosis, etc.). This dynamic is not limited to dermatology. How many Crohn’s patients have I met who say they left their conventional physicians with their standard treatments and now see a naturopath or acupuncturist? Their doctors don’t know they left, or why, because it’s impossible to remember someone who isn’t there, and their patients never told them why they left. These patients tell me they are now “doing better.”
Where evidence is outweighed by other patient considerations:
- topical 5-fluorouracil or imiquimod for superficial basal cells or noninvasive squamous cells in a patient who can’t reach the spot, doesn’t want to be bothered, or just wants the damned thing cut off.
Then, of course, there are cases where evidence is crucial. It’s just that, at the moment, I can’t think of many. Besides which, I’ve lost count of all the patients who had exhaustive food or patch testing, been found sensitive to any number of chemicals and foods – exotic or otherwise – dutifully avoided all of same, yet still break out intermittently and inscrutably, just like all my other atopics.
I’ve concluded that it must be me, or at least the small slice of the planet I work in. Maybe if I practice for 70 years instead of 40, or on five continents instead of the corner of just one, I will figure it all out.
To be clear: I am not a therapeutic nihilist. I want to use verifiably effective treatments for my patients, just as I wish such to be used on me when I need treatment. It’s just that instances in which compelling, decisive evidence makes a crucial difference don’t come up all that often. Evidence applies to populations, whereas I treat people, one at a time.
Meantime, I will muddle along, concerned that one drawback of the emphasis on “evidence” (i.e. statistics) not often noted is its contribution to depersonalizing medical practice, reducing the therapeutic interaction between two people to iterated instances of quantifiable throughput. If you can’t measure it, you didn’t do it and it doesn’t exist. But it does exist. Like every clinician, I see and do it every day.
As Hippocrates supposedly said: Life is short, and art long, opportunity fleeting, experimentations perilous, and judgment difficult.
Evidence notwithstanding, judgment remains difficult, mine and the patient’s.
Now that I’m done with evidence, please stay tuned for future columns where I take on motherhood (unacceptably gendered!) and apple pie (fattening!)
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
New research in otitis media
New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.
Transtympanic antibiotic delivery
Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.
Biofilms
Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.
Probiotics
The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.
Vaccines
The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.
Biomarkers.
Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.
Overdiagnosis
Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.
Immunity
The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].
New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.
Transtympanic antibiotic delivery
Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.
Biofilms
Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.
Probiotics
The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.
Vaccines
The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.
Biomarkers.
Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.
Overdiagnosis
Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.
Immunity
The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].
New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.
Transtympanic antibiotic delivery
Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.
Biofilms
Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.
Probiotics
The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.
Vaccines
The use of pneumococcal conjugate vaccines (PCVs) has reduced the frequency of AOM caused by Streptococcus pneumoniae. PCVs are not as effective against AOM as they are against invasive pneumococcal disease, but they still help a lot. However, because there are now at least 96 different serotypes of the pneumococcus based on different capsular types, we see a pattern of replacement of disease-causing strains by new strains within a few years of introduction of a new formulation. We started with 7 serotypes (Prevnar 7) in year 2000, and it was replaced by the current formulation with 13 serotypes (Prevnar 13) in 2010. Replacements have occurred again so vaccine companies are making new formulations for the future that include more serotypes, up to 20 serotypes. But, technically and feasibility-wise there is a limit to making such vaccines. A vaccine based on killed unencapsulated bacteria has been tested for safety and immunogenicity in young children. There is no test so far for prevention of AOM. Another type of vaccine based on proteins expressed by the pneumococcus that could be vaccine targets was tested in American Navajo children, and it failed to be as efficacious as hoped.
Biomarkers.
Due to recurrent AOM or persistent otitis media with effusion, about 15% of children in the United States receive tympanostomy tubes. Among those who receive tubes, about 20% go on to receive a second set of tubes, often with adenotonsillectomy. To find a biomarker that could identify children likely to require a second set of tubes, the fluid in the middle ear was tested when a first set of tubes were inserted. If bacteria were detected by polymerase chain reaction (PCR) testing or if a profile of specific inflammatory cytokines was measured, those results could be used to predict a high likelihood for a second set of tubes.
Overdiagnosis
Diagnosis of AOM is challenging in young children, in whom it most frequently occurs. The ear canal is typically about 3 mm wide, the child struggles during the examination, and diagnostic skills are not taught in training, resulting in a high overdiagnosis rate. I presented data that suggest too many children who are not truly otitis prone have been classified as otitis prone based on incorrect clinical diagnosis. My colleagues and I found that 30% of children reach the threshold of three episodes of AOM in 6 months or four within a year when diagnosed by community pediatricians, similar to many other studies. Validated otoscopists (trained by experts with diagnosis definitively proven as at least 85% accurate using tympanocentesis) classify 15% of children as otitis prone – half as many. If tympanocentesis is used to prove middle ear fluid has bacterial pathogens (about 95% yield a bacterial otopathogen using culture and PCR), then about 10% of children are classified as otitis prone – one-third as many. This suggests that children clinically diagnosed by community-based pediatricians are overdiagnosed with AOM, perhaps three times more often than true. And that leads to overuse of antibiotics and referrals for tympanostomy tube surgery more often than should occur. So we need to improve diagnostic methods beyond otoscopy. New types of imaging for the eardrum and middle ear using novel technologies are in early clinical trials.
Immunity
The notion that young children get AOM because of Eustachian tube dysfunction in their early years of life (horizontal anatomy) may be true, but there is more to the story. After 10 years of work, the scientists in my research group have shown that children in the first 3 years of life can have an immune system that is suppressed – it is poorly responsive to pathogens and routine pediatric vaccines. Many features resemble a neonatal immune system, beginning life with a suppressed immune system or being in cytokine storm from birth. We introduced the term “prolonged neonatal-like immune profile (PNIP)” to give a general description of the immune responses we have found in otitis-prone children. They outgrow this. So the immune maturation is delayed but not permanent. It is mostly resolved by age 3 years. We found problems in both innate and adaptive immunity. It may be that the main explanation for recurrent AOM in the first years of life is PNIP. Scientists from Australia also reported immunity problems in Aboriginal children and they are very otitis prone, often progressing to chronic suppurative otitis media. Animal model studies of AOM show inadequate innate and adaptive immunity importantly contribute to the infection as well.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Email him at [email protected].
Quality standards aim to improve worldwide spondyloarthritis care
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
REPORTING FROM EULAR 2019 CONGRESS