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NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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