MDedge Dermatology

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

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

Ted Bowsworth/MDedge News

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

Phase 2 study of orismilast

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

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

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

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

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

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

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

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

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

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

Phase 2 study of roflumilast

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bowsworth/MDedge News

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

Phase 2 study of orismilast

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

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

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

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

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

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

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

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

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

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

Phase 2 study of roflumilast

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bowsworth/MDedge News

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

Phase 2 study of orismilast

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

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

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

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

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

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

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

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

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

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

Phase 2 study of roflumilast

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The research was published online in Arthritis Care & Research.

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

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

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

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

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

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

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

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

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

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

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

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

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

The research was published online in Arthritis Care & Research.

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

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

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

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

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

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

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

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

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

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

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

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

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

The research was published online in Arthritis Care & Research.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Deuruxolitinib and the THRIVE studies

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

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

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

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

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

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

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

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

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

High participation in extension trial

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

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

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

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

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

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

Baricitinib and the BRAVE studies

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Deuruxolitinib and the THRIVE studies

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

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

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

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

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

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

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

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

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

High participation in extension trial

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

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

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

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

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

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

Baricitinib and the BRAVE studies

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Deuruxolitinib and the THRIVE studies

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

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

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

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

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

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

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

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

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

High participation in extension trial

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

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

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

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

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

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

Baricitinib and the BRAVE studies

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

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

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

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

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

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

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

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

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

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

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

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Emergency nurse Stephanee Beggs, RN, BSN, has made more than $2 million in three years selling her handwritten guides to study for the National Council Licensure Examination (NCLEX).

Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.

The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.

Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.

Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.

“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”

Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.

Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.

Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”

One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”

Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.

“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”

She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
 

Nursing groups weigh in

Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”

For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.

But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.

“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”

The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
 

‘Not cutting corners’

As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”

“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”

She said she sees her guides as a supplement to learning, not a replacement.

“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”

Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.

The answer is no, at least not yet.

“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.  

“I love everything about both aspects, so it’s hard for me to choose.”

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

Emergency nurse Stephanee Beggs, RN, BSN, has made more than $2 million in three years selling her handwritten guides to study for the National Council Licensure Examination (NCLEX).

Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.

The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.

Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.

Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.

“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”

Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.

Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.

Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”

One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”

Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.

“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”

She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
 

Nursing groups weigh in

Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”

For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.

But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.

“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”

The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
 

‘Not cutting corners’

As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”

“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”

She said she sees her guides as a supplement to learning, not a replacement.

“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”

Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.

The answer is no, at least not yet.

“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.  

“I love everything about both aspects, so it’s hard for me to choose.”

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

Emergency nurse Stephanee Beggs, RN, BSN, has made more than $2 million in three years selling her handwritten guides to study for the National Council Licensure Examination (NCLEX).

Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.

The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.

Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.

Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.

“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”

Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.

Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.

Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”

One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”

Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.

“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”

She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
 

Nursing groups weigh in

Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”

For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.

But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.

“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”

The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
 

‘Not cutting corners’

As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”

“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”

She said she sees her guides as a supplement to learning, not a replacement.

“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”

Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.

The answer is no, at least not yet.

“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.  

“I love everything about both aspects, so it’s hard for me to choose.”

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

Key clinical point: Compared with mild atopic dermatitis (AD), severe AD results in an increased risk for overall morbidity.

Major finding: Patients with severe vs mild AD had a significantly increased risk for other dermatitis, extragenital herpes, urticaria, impetigo, cellulitis, varicella zoster virus, abscess, sepsis, conjunctivitis, alopecia areata, asthma, allergic rhinitis and conjunctivitis, stress-related and somatoform diseases, intervertebral disc disorders, osteoporosis, and lymphomas (all P < .001), as well as condylomas, rosacea, certain psychiatric disorders, migraine, sleep apnea, other sleep disorders, hypertension, atherosclerosis, enthesopathies, and drug-induced cataract (all P < .05). However, patients with moderate or severe vs mild AD had a lower risk for prostate cancer (P < .05).

Study details: The data come from a retrospective real-world cohort study including 124,038 patients with mild (n = 53,046), moderate (n = 46,296), or severe (n = 24,696) AD.

Disclosures: This study was sponsored by AbbVie. Some authors reported ties, including employment and stock ownership, with AbbVie and others.

Source: Kiiski V et al. Effect of disease severity on comorbid conditions in atopic dermatitis: Nationwide registry-based investigation in Finnish adults. Acta Derm Venereol. 2023;103:adv00882 (Mar 8). Doi: 10.2340/actadv.v103.4447

Key clinical point: Compared with mild atopic dermatitis (AD), severe AD results in an increased risk for overall morbidity.

Major finding: Patients with severe vs mild AD had a significantly increased risk for other dermatitis, extragenital herpes, urticaria, impetigo, cellulitis, varicella zoster virus, abscess, sepsis, conjunctivitis, alopecia areata, asthma, allergic rhinitis and conjunctivitis, stress-related and somatoform diseases, intervertebral disc disorders, osteoporosis, and lymphomas (all P < .001), as well as condylomas, rosacea, certain psychiatric disorders, migraine, sleep apnea, other sleep disorders, hypertension, atherosclerosis, enthesopathies, and drug-induced cataract (all P < .05). However, patients with moderate or severe vs mild AD had a lower risk for prostate cancer (P < .05).

Study details: The data come from a retrospective real-world cohort study including 124,038 patients with mild (n = 53,046), moderate (n = 46,296), or severe (n = 24,696) AD.

Disclosures: This study was sponsored by AbbVie. Some authors reported ties, including employment and stock ownership, with AbbVie and others.

Source: Kiiski V et al. Effect of disease severity on comorbid conditions in atopic dermatitis: Nationwide registry-based investigation in Finnish adults. Acta Derm Venereol. 2023;103:adv00882 (Mar 8). Doi: 10.2340/actadv.v103.4447

Key clinical point: Compared with mild atopic dermatitis (AD), severe AD results in an increased risk for overall morbidity.

Major finding: Patients with severe vs mild AD had a significantly increased risk for other dermatitis, extragenital herpes, urticaria, impetigo, cellulitis, varicella zoster virus, abscess, sepsis, conjunctivitis, alopecia areata, asthma, allergic rhinitis and conjunctivitis, stress-related and somatoform diseases, intervertebral disc disorders, osteoporosis, and lymphomas (all P < .001), as well as condylomas, rosacea, certain psychiatric disorders, migraine, sleep apnea, other sleep disorders, hypertension, atherosclerosis, enthesopathies, and drug-induced cataract (all P < .05). However, patients with moderate or severe vs mild AD had a lower risk for prostate cancer (P < .05).

Study details: The data come from a retrospective real-world cohort study including 124,038 patients with mild (n = 53,046), moderate (n = 46,296), or severe (n = 24,696) AD.

Disclosures: This study was sponsored by AbbVie. Some authors reported ties, including employment and stock ownership, with AbbVie and others.

Source: Kiiski V et al. Effect of disease severity on comorbid conditions in atopic dermatitis: Nationwide registry-based investigation in Finnish adults. Acta Derm Venereol. 2023;103:adv00882 (Mar 8). Doi: 10.2340/actadv.v103.4447

Key clinical point: Stratum corneum (SC) lipid and cytokine levels in infants aged 2 months can predict the future onset of atopic dermatitis (AD) up to 2 years of age.

Major finding: The SC levels of protein-bound ceramides were decreased (P = .0058), whereas those of unsaturated sphingomyelin (P < .0001), thymic stromal lymphopoietin (P = .0032), and interleukin-13 (IL13; P < .0001) increased in infants with vs without a family history of atopic diseases. A combination of family history and high IL13, high 26:1-sphingomyelin, and low O30:0(C22S)-ceramide levels had a strong predictive power for AD onset by 2 years of age (adjusted odds ratio 54.0; 95% CI 9.2-317.5).

Study details: This observational study included 111 asymptomatic infants with or without a family history of atopic diseases who underwent skin tape strip analysis at 2 months of age.

Disclosures: This study was funded by Edelstein Family Chair of Pediatric Allergy-Immunology at National Jewish Health, Denver, Colorado, and the Korea Environment Industry and Technology Institute (KEITI) through Environmental Health Action Program, funded by Korea Ministry of Environment. Some authors reported ties with various organizations.

Source: Berdyshev E et al. Stratum corneum lipid and cytokine biomarkers at two months of age predict the future onset of atopic dermatitis. J Allergy Clin Immunol. 2023 (Feb 22). Doi: 10.1016/j.jaci.2023.02.013

Key clinical point: Stratum corneum (SC) lipid and cytokine levels in infants aged 2 months can predict the future onset of atopic dermatitis (AD) up to 2 years of age.

Major finding: The SC levels of protein-bound ceramides were decreased (P = .0058), whereas those of unsaturated sphingomyelin (P < .0001), thymic stromal lymphopoietin (P = .0032), and interleukin-13 (IL13; P < .0001) increased in infants with vs without a family history of atopic diseases. A combination of family history and high IL13, high 26:1-sphingomyelin, and low O30:0(C22S)-ceramide levels had a strong predictive power for AD onset by 2 years of age (adjusted odds ratio 54.0; 95% CI 9.2-317.5).

Study details: This observational study included 111 asymptomatic infants with or without a family history of atopic diseases who underwent skin tape strip analysis at 2 months of age.

Disclosures: This study was funded by Edelstein Family Chair of Pediatric Allergy-Immunology at National Jewish Health, Denver, Colorado, and the Korea Environment Industry and Technology Institute (KEITI) through Environmental Health Action Program, funded by Korea Ministry of Environment. Some authors reported ties with various organizations.

Source: Berdyshev E et al. Stratum corneum lipid and cytokine biomarkers at two months of age predict the future onset of atopic dermatitis. J Allergy Clin Immunol. 2023 (Feb 22). Doi: 10.1016/j.jaci.2023.02.013

Key clinical point: Stratum corneum (SC) lipid and cytokine levels in infants aged 2 months can predict the future onset of atopic dermatitis (AD) up to 2 years of age.

Major finding: The SC levels of protein-bound ceramides were decreased (P = .0058), whereas those of unsaturated sphingomyelin (P < .0001), thymic stromal lymphopoietin (P = .0032), and interleukin-13 (IL13; P < .0001) increased in infants with vs without a family history of atopic diseases. A combination of family history and high IL13, high 26:1-sphingomyelin, and low O30:0(C22S)-ceramide levels had a strong predictive power for AD onset by 2 years of age (adjusted odds ratio 54.0; 95% CI 9.2-317.5).

Study details: This observational study included 111 asymptomatic infants with or without a family history of atopic diseases who underwent skin tape strip analysis at 2 months of age.

Disclosures: This study was funded by Edelstein Family Chair of Pediatric Allergy-Immunology at National Jewish Health, Denver, Colorado, and the Korea Environment Industry and Technology Institute (KEITI) through Environmental Health Action Program, funded by Korea Ministry of Environment. Some authors reported ties with various organizations.

Source: Berdyshev E et al. Stratum corneum lipid and cytokine biomarkers at two months of age predict the future onset of atopic dermatitis. J Allergy Clin Immunol. 2023 (Feb 22). Doi: 10.1016/j.jaci.2023.02.013