Pharmacology

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Human insulin can be left unrefrigerated for much longer than previously thought, findings from a new Cochrane review suggest.

The review included 17 studies in 22 published articles and additional unpublished information from major insulin manufacturers. The data suggest it is possible to store unopened short- and intermediate-acting human insulin vials, pens/cartridges or prefilled plastic syringes at temperatures up to 25 °C (77 °F) for a maximum of 6 months and up to 37 °C (98.6 °F) for a maximum of 2 months without a clinically relevant loss of insulin potency.

Two studies found small decrements in potency at higher temperatures and/or longer durations unrefrigerated, but the rest did not.

This contrasts with current guidance and labeling that advises storing unopened human insulin at temperatures between 2 °C (35.6 °F) and 8°C (46.4 °F), necessitating refrigeration. Once the vial or pen cartridge is opened, the guidance is to store at “room temperature” and use within about 4-6 weeks.

The recommendations vary, however, and there is no clear consensus on how human insulin should be stored in settings where reliable refrigeration can’t be guaranteed, such as low-income countries, those affected by extreme heat, or areas of conflict or natural disasters. Such areas are home to growing numbers of people with diabetes, according to the Cochrane Database of Systematic Reviews report, published online.

The review also found that oscillating temperatures between 25 °C (77 °F) and 37 °C (98.6 °F), typical of daytime and nighttime fluctuations in tropical countries, for up to 3 months do not result in clinically relevant loss of insulin activity for short-acting, intermediate-acting, or mixed human insulin.   

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being,” the study’s lead author, Bernd Richter, MD, of the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany, said in a statement.

In addition, one small pilot clinical study showed that human insulin stored for 6 weeks in an unglazed clay pot with temperatures ranging between 25 °C (77 °F) and 27°C (80.6 °F) did not result in differences in plasma glucose–lowering in eight healthy volunteers, compared with refrigerator-stored insulin. “With the help of simple cooling devices for insulin storage such as clay pots, it is possible to effectively reduce high outside temperatures in many high-temperature regions of the world,” wrote Dr. Richter and colleagues Brenda Bongaerts, PhD, and Maria-Inti Metzendorf, also from Heinrich-Heine-University.

Asked to comment, Leonardo Scapozza, PhD, of the School of Pharmaceutical Sciences at the University of Geneva, Switzerland, said that these findings align with a study he published in 2021.   

“Indeed ... we have done a small-scale study by analyzing the insulin coming back from the field and showing that insulin potency and stability was conserved. An extended clinical study where the insulin is submitted to varying controlled condition is not possible and ethically debatable. But an extended study where patients are given a log tag to monitor their real storage condition and the remaining samples are collected back and sent back for analysis in a specialized lab would be very good to further confirm the [conclusions],” said Dr. Scapozza, who was not part of Dr. Richter’s team on this review. 

While the issue of insulin refrigeration is less urgent in higher-income countries, it does arise, as in situations where people accidentally leave their unopened insulin out of the refrigerator or when they carry backup insulin while traveling.

The Cochrane Review excluded studies of insulin analogs, used in most developed countries, but Dr. Scapozza’s study had included them. “We observed the same stability as the ones used in low-income countries.” He added that his data combined with those in the new report provide evidence that would make it “possible to better and optimally use the available insulin that is becoming more and more costly.”

Dr. Scapozza also told this news organization that after he presented his data to Médecins Sans Frontières (Doctors Without Borders), he heard from a collaborator with that group who has diabetes. “He always used his insulin for his own treatment when he was in the field working and his insulin pen was in his backpack or pocket and his treatment was working. After hearing the data, he was very happy because he got a scientific explanation why his treatment was working, whether he was in Switzerland or during his mission in the camps submitted to the same condition of storage as any other patient in low income countries.”

Dr. Richter and Dr. Scapozza report no relevant financial relationships.

A version of this article appeared on Medscape.com.