Atopic Dermatitis

Key clinical point: Early application of emollients can effectively prevent atopic dermatitis (AD) in infants, with emollient emulsion seeming an optimal treatment option in infancy compared with creams or mixed emollients.

Major finding: The incidence of AD was significantly lower in high-risk infants receiving early emollients vs standard care (risk ratio 0.64; 95% CI 0.47-0.88), with surface under the cumulative ranking curve analysis revealing emollient emulsion (82.6%) as the optimal treatment for AD prevention in infants, followed by mixed emollient (77.4%) and emollient cream (21.9%).

Study details: This was a systematic review and network meta-analysis of 11 randomized controlled trials including 3483 infants without AD who received either prophylactic emollients (cream, emulsion, or mixed types) or standard care.

Disclosures: This study was supported by the Key Research and Development Project of Xinjiang Uygur Autonomous Region, China. The authors declared no  conflicts of interest.

Source: Liang J, Hu F et al. Systematic review and network meta‐analysis of different types of emollient for the prevention of atopic dermatitis in infants. J Eur Acad Dermatol Venereol. 2022 (Nov 23). Doi: 10.1111/jdv.18688

Key clinical point: Early application of emollients can effectively prevent atopic dermatitis (AD) in infants, with emollient emulsion seeming an optimal treatment option in infancy compared with creams or mixed emollients.

Major finding: The incidence of AD was significantly lower in high-risk infants receiving early emollients vs standard care (risk ratio 0.64; 95% CI 0.47-0.88), with surface under the cumulative ranking curve analysis revealing emollient emulsion (82.6%) as the optimal treatment for AD prevention in infants, followed by mixed emollient (77.4%) and emollient cream (21.9%).

Study details: This was a systematic review and network meta-analysis of 11 randomized controlled trials including 3483 infants without AD who received either prophylactic emollients (cream, emulsion, or mixed types) or standard care.

Disclosures: This study was supported by the Key Research and Development Project of Xinjiang Uygur Autonomous Region, China. The authors declared no  conflicts of interest.

Source: Liang J, Hu F et al. Systematic review and network meta‐analysis of different types of emollient for the prevention of atopic dermatitis in infants. J Eur Acad Dermatol Venereol. 2022 (Nov 23). Doi: 10.1111/jdv.18688

Key clinical point: Early application of emollients can effectively prevent atopic dermatitis (AD) in infants, with emollient emulsion seeming an optimal treatment option in infancy compared with creams or mixed emollients.

Major finding: The incidence of AD was significantly lower in high-risk infants receiving early emollients vs standard care (risk ratio 0.64; 95% CI 0.47-0.88), with surface under the cumulative ranking curve analysis revealing emollient emulsion (82.6%) as the optimal treatment for AD prevention in infants, followed by mixed emollient (77.4%) and emollient cream (21.9%).

Study details: This was a systematic review and network meta-analysis of 11 randomized controlled trials including 3483 infants without AD who received either prophylactic emollients (cream, emulsion, or mixed types) or standard care.

Disclosures: This study was supported by the Key Research and Development Project of Xinjiang Uygur Autonomous Region, China. The authors declared no  conflicts of interest.

Source: Liang J, Hu F et al. Systematic review and network meta‐analysis of different types of emollient for the prevention of atopic dermatitis in infants. J Eur Acad Dermatol Venereol. 2022 (Nov 23). Doi: 10.1111/jdv.18688

Key clinical point: Ruxolitinib cream demonstrated effective disease control and was well tolerated in patients with atopic dermatitis (AD) during 44 weeks of as-needed treatment.

Major finding: At week 52, 74.1%-77.8% of patients had an Investigator’s Global Assessment score of 0/1, with the mean affected body surface area being 1.4%-1.8%. Treatment-related adverse events were reported in 8.7%/7.4% of patients on 0.75%/1.5% ruxolitinib and in 2.0%/6.1% of those who switched from vehicle to 0.75%/1.5% ruxolitinib, respectively.

Study details: This study analyzed pooled data from two phase 3 studies, TRuE-AD1 and TRuE-AD2, including 1249 patients aged ≥12 years with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle for 8 weeks; thereafter, the vehicle group patients were re-assigned to receive either strength ruxolitinib cream for 44 weeks.

Disclosures: This study was funded by Incyte Corporation, U.S. Some authors reported ties with various sources, including Incyte. Four authors declared being current or former employees and shareholders of Incyte.

Source: Papp K et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies. J Am Acad Dermatol. 2022 (Nov 25). Doi: 10.1016/j.jaad.2022.09.060

Key clinical point: Ruxolitinib cream demonstrated effective disease control and was well tolerated in patients with atopic dermatitis (AD) during 44 weeks of as-needed treatment.

Major finding: At week 52, 74.1%-77.8% of patients had an Investigator’s Global Assessment score of 0/1, with the mean affected body surface area being 1.4%-1.8%. Treatment-related adverse events were reported in 8.7%/7.4% of patients on 0.75%/1.5% ruxolitinib and in 2.0%/6.1% of those who switched from vehicle to 0.75%/1.5% ruxolitinib, respectively.

Study details: This study analyzed pooled data from two phase 3 studies, TRuE-AD1 and TRuE-AD2, including 1249 patients aged ≥12 years with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle for 8 weeks; thereafter, the vehicle group patients were re-assigned to receive either strength ruxolitinib cream for 44 weeks.

Disclosures: This study was funded by Incyte Corporation, U.S. Some authors reported ties with various sources, including Incyte. Four authors declared being current or former employees and shareholders of Incyte.

Source: Papp K et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies. J Am Acad Dermatol. 2022 (Nov 25). Doi: 10.1016/j.jaad.2022.09.060

Key clinical point: Ruxolitinib cream demonstrated effective disease control and was well tolerated in patients with atopic dermatitis (AD) during 44 weeks of as-needed treatment.

Major finding: At week 52, 74.1%-77.8% of patients had an Investigator’s Global Assessment score of 0/1, with the mean affected body surface area being 1.4%-1.8%. Treatment-related adverse events were reported in 8.7%/7.4% of patients on 0.75%/1.5% ruxolitinib and in 2.0%/6.1% of those who switched from vehicle to 0.75%/1.5% ruxolitinib, respectively.

Study details: This study analyzed pooled data from two phase 3 studies, TRuE-AD1 and TRuE-AD2, including 1249 patients aged ≥12 years with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle for 8 weeks; thereafter, the vehicle group patients were re-assigned to receive either strength ruxolitinib cream for 44 weeks.

Disclosures: This study was funded by Incyte Corporation, U.S. Some authors reported ties with various sources, including Incyte. Four authors declared being current or former employees and shareholders of Incyte.

Source: Papp K et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies. J Am Acad Dermatol. 2022 (Nov 25). Doi: 10.1016/j.jaad.2022.09.060

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: Specific targeting of interleukin-13 alone with tralokinumab improved microbial diversity and reduced Staphylococcus aureus abundance in the lesional skin in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The 16-week tralokinumab treatment reduced S. aureus abundance by 20.7-fold (P < .0001), whereas placebo led to a non-statistically significant reduction. Tralokinumab also led to a significant increase in microbial diversity as early as week 8 (P < .001) and also at week 16 (P < .05).

Study details: The data come from the phase 3 ECZTRA 1 trial including 802 patients with moderate-to-severe AD who were randomly assigned to receive 300 mg subcutaneous tralokinumab or placebo.

Disclosures: This study and the ECZTRA 1 trial were funded by LEO Pharma A/S. Some authors declared serving as speakers, consultants, investigators, scientific advisors, or clinical study investigators or receiving institutional research grants from various sources, including LEO Pharma.

Source: Beck LA et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J Am Acad Dermatol. 2022 (Dec 2). Doi: 10.1016/j.jaad.2022.11.047

Key clinical point: An exposure to topical calcineurin inhibitors did not increase the risk for cancer in patients with atopic dermatitis (AD), with findings being similar among infants, children, and adults.

Major finding: Compared with no exposure, topical calcineurin inhibitor exposure was not associated with an increased risk for cancer (odds ratio [OR] 1.03; 95% credible interval [CrI] 0.94-1.11), with neither pimecrolimus (OR 1.05; 95% CrI 0.94-1.15) nor tacrolimus (OR 0.99; 95% CrI 0.89-1.09) use revealing any association with increased cancer risk, across all age groups.

Study details: This was a systematic review and meta-analysis of 110 unique studies (52 randomized controlled trials and 69 nonrandomized studies) including 3.4 million patients with AD followed-up for a mean of 11 months.

Disclosures: This study was funded by the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology. L Schneider declared receiving consulting fees and payments to her institutions from, serving on data safety monitoring and advisory boards for, and holding stock or stock options in various sources.

Source: Devasenapathy N et al for the AAAAI/ACAAI Joint Task Force on Practice Parameters for Atopic Dermatitis Guideline Development Group. Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: A systematic review and meta-analysis. Lancet Child Adolesc Health. 2022 (Nov 9). Doi: 10.1016/S2352-4642(22)00283-8

Key clinical point: An exposure to topical calcineurin inhibitors did not increase the risk for cancer in patients with atopic dermatitis (AD), with findings being similar among infants, children, and adults.

Major finding: Compared with no exposure, topical calcineurin inhibitor exposure was not associated with an increased risk for cancer (odds ratio [OR] 1.03; 95% credible interval [CrI] 0.94-1.11), with neither pimecrolimus (OR 1.05; 95% CrI 0.94-1.15) nor tacrolimus (OR 0.99; 95% CrI 0.89-1.09) use revealing any association with increased cancer risk, across all age groups.

Study details: This was a systematic review and meta-analysis of 110 unique studies (52 randomized controlled trials and 69 nonrandomized studies) including 3.4 million patients with AD followed-up for a mean of 11 months.

Disclosures: This study was funded by the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology. L Schneider declared receiving consulting fees and payments to her institutions from, serving on data safety monitoring and advisory boards for, and holding stock or stock options in various sources.

Source: Devasenapathy N et al for the AAAAI/ACAAI Joint Task Force on Practice Parameters for Atopic Dermatitis Guideline Development Group. Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: A systematic review and meta-analysis. Lancet Child Adolesc Health. 2022 (Nov 9). Doi: 10.1016/S2352-4642(22)00283-8

Key clinical point: An exposure to topical calcineurin inhibitors did not increase the risk for cancer in patients with atopic dermatitis (AD), with findings being similar among infants, children, and adults.

Major finding: Compared with no exposure, topical calcineurin inhibitor exposure was not associated with an increased risk for cancer (odds ratio [OR] 1.03; 95% credible interval [CrI] 0.94-1.11), with neither pimecrolimus (OR 1.05; 95% CrI 0.94-1.15) nor tacrolimus (OR 0.99; 95% CrI 0.89-1.09) use revealing any association with increased cancer risk, across all age groups.

Study details: This was a systematic review and meta-analysis of 110 unique studies (52 randomized controlled trials and 69 nonrandomized studies) including 3.4 million patients with AD followed-up for a mean of 11 months.

Disclosures: This study was funded by the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology. L Schneider declared receiving consulting fees and payments to her institutions from, serving on data safety monitoring and advisory boards for, and holding stock or stock options in various sources.

Source: Devasenapathy N et al for the AAAAI/ACAAI Joint Task Force on Practice Parameters for Atopic Dermatitis Guideline Development Group. Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: A systematic review and meta-analysis. Lancet Child Adolesc Health. 2022 (Nov 9). Doi: 10.1016/S2352-4642(22)00283-8

Key clinical point: Treatment with rocatinlimab, a novel monoclonal antibody, significantly improved disease severity at all dosing regimens in patients with moderate-to-severe atopic dermatitis (AD) inadequately controlled with topical therapy, which was maintained in most patients even after treatment discontinuation.

Major finding: The least-squares mean percent reductions in the Eczema Area and Severity Index at week 16 were significantly greater with 150 mg rocatinlimab every 4 weeks vs placebo (−48.3% vs −15.0%; P  =  .0003), with all other active rocatinlimab dose regimens vs placebo showing improvement (all P < .05) and most patients showing sustained response during off-drug follow-up.

Study details: The data come from a multicenter phase 2b study including 274 patients with moderate-to-severe AD and inadequate response or intolerance to topical medications and who were randomly assigned to receive rocatinlimab or placebo.

Disclosures: This study was funded by Kyowa Kirin. Some authors reported ties with various sources, including Kyowa Kirin. E Esfandiari declared being an employee of Kyowa Kirin.

Source: Guttman-Yassky E et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: A multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2022 (Dec 9). Doi: 10.1016/S0140-6736(22)02037-2

Key clinical point: Treatment with rocatinlimab, a novel monoclonal antibody, significantly improved disease severity at all dosing regimens in patients with moderate-to-severe atopic dermatitis (AD) inadequately controlled with topical therapy, which was maintained in most patients even after treatment discontinuation.

Major finding: The least-squares mean percent reductions in the Eczema Area and Severity Index at week 16 were significantly greater with 150 mg rocatinlimab every 4 weeks vs placebo (−48.3% vs −15.0%; P  =  .0003), with all other active rocatinlimab dose regimens vs placebo showing improvement (all P < .05) and most patients showing sustained response during off-drug follow-up.

Study details: The data come from a multicenter phase 2b study including 274 patients with moderate-to-severe AD and inadequate response or intolerance to topical medications and who were randomly assigned to receive rocatinlimab or placebo.

Disclosures: This study was funded by Kyowa Kirin. Some authors reported ties with various sources, including Kyowa Kirin. E Esfandiari declared being an employee of Kyowa Kirin.

Source: Guttman-Yassky E et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: A multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2022 (Dec 9). Doi: 10.1016/S0140-6736(22)02037-2

Key clinical point: Treatment with rocatinlimab, a novel monoclonal antibody, significantly improved disease severity at all dosing regimens in patients with moderate-to-severe atopic dermatitis (AD) inadequately controlled with topical therapy, which was maintained in most patients even after treatment discontinuation.

Major finding: The least-squares mean percent reductions in the Eczema Area and Severity Index at week 16 were significantly greater with 150 mg rocatinlimab every 4 weeks vs placebo (−48.3% vs −15.0%; P  =  .0003), with all other active rocatinlimab dose regimens vs placebo showing improvement (all P < .05) and most patients showing sustained response during off-drug follow-up.

Study details: The data come from a multicenter phase 2b study including 274 patients with moderate-to-severe AD and inadequate response or intolerance to topical medications and who were randomly assigned to receive rocatinlimab or placebo.

Disclosures: This study was funded by Kyowa Kirin. Some authors reported ties with various sources, including Kyowa Kirin. E Esfandiari declared being an employee of Kyowa Kirin.

Source: Guttman-Yassky E et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: A multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2022 (Dec 9). Doi: 10.1016/S0140-6736(22)02037-2

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

A registry-based study provides further evidence that treatment with dupilumab significantly reduces severity and symptoms of atopic dermatitis (AD) in clinical practice.

Dupilumab also decreased severity-associated biomarkers in pediatric patients with moderate to severe AD, researchers in the Netherlands reported.

Obtaining serum biomarkers is not the current standard in everyday practice, but studying them may improve understanding of who might respond best to dupilumab, said Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health in Denver, in an email comment to this news organization.

“AD is heterogeneous, as each patient may have different presentations and underlying biology,” said Dr. Hui, who wasn’t involved in the research. “Studying biomarkers can eventually assist us in providing targeted therapy to each individual patient.”

Dr. Hui added, “As blood biomarkers can inform us of severity and treatment response, we can be hopeful that this will assist us in the management of AD patients in the future.”
 

Examining effect on disease severity

Dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is approved in Europe and the United States to treat moderate to severe AD in patients 6 months of age or older, and to treat certain other inflammatory conditions.

Phase 3 studies show that dupilumab is effective for improving AD symptoms and quality of life in pediatric patients, but few clinical practice studies have researched the effect of the therapy on severity- and disease-related biomarkers in this population, the study authors write.

The study was published online in Pediatric Allergy Immunology.

In a new study, a team led by Esmé Kamphuis, MD, of the University of Groningen, the Netherlands, and colleagues evaluated the efficacy and safety of a 28-week dupilumab treatment course in 61 pediatric patients with moderate to severe AD. Additionally, the investigators examined the effect of this treatment regimen on serum biomarkers associated with disease severity.

Patients in the study were registered in the multicenter BioDay registry, which includes patients with moderate to severe AD receiving biologics or small-molecule agents. The AD cohort included children between 6 and 12 years of age (n = 16) and adolescents between 12 and less than 18 years of age (n = 45), all of whom received dupilumab on a dosing regimen indicated by age and body weight.

Over one-third (36.1%) of dupilumab-treated patients achieved an Investigator Global Assessment score of “almost clear” by 28 weeks of treatment. Approximately 75.4% of patients reached an Eczema Area and Severity Index (EASI) of 50, 49.2% reached EASI-75, and 24.6% reached EASI-90 at the 7-month follow-up.

Among patient-reported outcomes, 84.7% experienced improvements of 4 or more points on the Patient-Oriented Eczema Measure after the 28-week dupilumab treatment. In addition, improvements of 4 or more points on the Numeric Rating Scale for pruritus and pain were achieved by 45.3% and 77.4% of patients, respectively.

The most frequently reported side effects included conjunctivitis (n = 10) and headache (n = 4).

Of the 19 severity-associated serum biomarkers measured at baseline, week 4, and week 16, markers related to AD severity and treatment response significantly decreased during treatment (thymus- and activation-regulated chemokine, pulmonary and activation-regulated chemokine, periostin, soluble IL-2 receptor alpha).

A predicted EASI, calculated from selected biomarkers, demonstrated a significant association with disease severity in the cohort.
 

Implications for practice

When asked to comment on the study findings, Raegan Hunt, MD, the division chief of pediatric dermatology at Texas Children’s Hospital in Houston, said it is important to validate the changes in AD serum biomarkers in pediatric patients on dupilumab therapy, given that this treatment has historically been better studied in adults.

“This study adds to daily practice outcomes data, which in many cases is more relevant to the everyday care of patients than structured clinical trial data,” said Dr. Hunt, an associate professor at the Baylor College of Medicine, Houston.

Dr. Hunt, who didn’t participate in the study, noted that more research is needed on the adverse effects of dupilumab in the pediatric AD population.

Dr. Hui added that there is a lack of clear understanding of the exact underlying mechanisms for certain side effects, such as conjunctivitis, warranting further study.

The study’s BioDay registry is funded by Sanofi/Regeneron, AbbVie, Leo Pharma, Pfizer, and Eli Lilly. Several study coauthors report relationships with several pharmaceutical companies. Dr. Hunt and Dr. Hui report no relevant financial relationships.

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

A maternal or parental history of atopic dermatitis (AD) or asthma is associated with an increased risk of AD in offspring in the first 2 years of life, an analysis of a large birth cohort found.

“The prevalence of AD in children has increased dramatically in recent years, and most studies reporting the impact of parental atopic history on AD are based on older data,” wrote the study authors, led by Cathal O’Connor, MD. “Given the recent interest in early intervention to prevent AD and other allergic diseases, enhanced early identification of infants at risk of AD is increasingly important.”

The detailed analysis of AD risk associated with parental atopy in early life “may help to risk stratify infants to optimize early interventions for prevention or early treatment of AD,” they wrote.

LucaLorenzelli/Thinkstock

The study was published in Pediatric Dermatology.

For the analysis, Dr. O’Connor of the department of pediatrics and child health at University College Cork (Ireland) and colleagues conducted a secondary analysis of the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study.

The study recruited 2,183 healthy first-born babies between August 2009 and October 2011 to examine the effects of environmental factors during pregnancy and infancy on childhood health and development. Skin barrier assessments were performed at birth, 2 months, 6 months, 12 months, and 24 months using a validated open chamber system to measure transepidermal water loss.

Parental atopy was self-reported at 2 months. Parents were asked at 2 months if the infant had an “itchy rash on the face or in the folds of the arms or legs,” as a screening question for AD. Experienced health care personnel used UK Working Party criteria to diagnose AD at 6, 12, and 24 months.

Complete data on AD status was available for 1,505 children in the cohort. Dr. O’Connor and colleagues calculated an overall AD prevalence of 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months.

Overall prevalence of AD was highest at 6 months. The study showed a similar or slightly higher impact of paternal atopy on offspring AD development, compared to maternal atopy.

Multivariable logistic regression analysis revealed that the odds of AD were 1.57 at 6 months and 1.66 at 12 months for maternal AD; 1.90 at 6 months and 1.85 at 24 months for paternal AD; 1.76 at 6 months and 1.75 at 12 months for maternal asthma; and 1.70 at 6 months, 1.86 at 12 months, and 1.99 at 24 months for paternal asthma.

“Parental allergic rhinitis was not associated with AD in offspring in the first 2 years, except for maternal rhinitis at 24 months [an adjusted odds ratio of 1.79],” the authors wrote. “The genetic predisposition to allergic rhinitis, given the key role of aeroallergen sensitization in its pathogenesis, may not be associated with early onset AD, but may have a greater impact in later onset or persistent AD.”

The authors acknowledged certain limitations of the study, including the fact that it was a secondary data analysis, and that parental AD, asthma, and rhinitis were self-reported, “which may reduce reliability and may contribute to the differences seen between the impact of maternal and paternal reported atopy on offspring,” they wrote. “Data on siblings were not captured, as participants in the study were first-born children. Filaggrin mutational analysis was not performed, which would have provided richer detail.”

A maternal or parental history of atopic dermatitis (AD) or asthma is associated with an increased risk of AD in offspring in the first 2 years of life, an analysis of a large birth cohort found.

“The prevalence of AD in children has increased dramatically in recent years, and most studies reporting the impact of parental atopic history on AD are based on older data,” wrote the study authors, led by Cathal O’Connor, MD. “Given the recent interest in early intervention to prevent AD and other allergic diseases, enhanced early identification of infants at risk of AD is increasingly important.”

The detailed analysis of AD risk associated with parental atopy in early life “may help to risk stratify infants to optimize early interventions for prevention or early treatment of AD,” they wrote.

LucaLorenzelli/Thinkstock

The study was published in Pediatric Dermatology.

For the analysis, Dr. O’Connor of the department of pediatrics and child health at University College Cork (Ireland) and colleagues conducted a secondary analysis of the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study.

The study recruited 2,183 healthy first-born babies between August 2009 and October 2011 to examine the effects of environmental factors during pregnancy and infancy on childhood health and development. Skin barrier assessments were performed at birth, 2 months, 6 months, 12 months, and 24 months using a validated open chamber system to measure transepidermal water loss.

Parental atopy was self-reported at 2 months. Parents were asked at 2 months if the infant had an “itchy rash on the face or in the folds of the arms or legs,” as a screening question for AD. Experienced health care personnel used UK Working Party criteria to diagnose AD at 6, 12, and 24 months.

Complete data on AD status was available for 1,505 children in the cohort. Dr. O’Connor and colleagues calculated an overall AD prevalence of 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months.

Overall prevalence of AD was highest at 6 months. The study showed a similar or slightly higher impact of paternal atopy on offspring AD development, compared to maternal atopy.

Multivariable logistic regression analysis revealed that the odds of AD were 1.57 at 6 months and 1.66 at 12 months for maternal AD; 1.90 at 6 months and 1.85 at 24 months for paternal AD; 1.76 at 6 months and 1.75 at 12 months for maternal asthma; and 1.70 at 6 months, 1.86 at 12 months, and 1.99 at 24 months for paternal asthma.

“Parental allergic rhinitis was not associated with AD in offspring in the first 2 years, except for maternal rhinitis at 24 months [an adjusted odds ratio of 1.79],” the authors wrote. “The genetic predisposition to allergic rhinitis, given the key role of aeroallergen sensitization in its pathogenesis, may not be associated with early onset AD, but may have a greater impact in later onset or persistent AD.”

The authors acknowledged certain limitations of the study, including the fact that it was a secondary data analysis, and that parental AD, asthma, and rhinitis were self-reported, “which may reduce reliability and may contribute to the differences seen between the impact of maternal and paternal reported atopy on offspring,” they wrote. “Data on siblings were not captured, as participants in the study were first-born children. Filaggrin mutational analysis was not performed, which would have provided richer detail.”

A maternal or parental history of atopic dermatitis (AD) or asthma is associated with an increased risk of AD in offspring in the first 2 years of life, an analysis of a large birth cohort found.

“The prevalence of AD in children has increased dramatically in recent years, and most studies reporting the impact of parental atopic history on AD are based on older data,” wrote the study authors, led by Cathal O’Connor, MD. “Given the recent interest in early intervention to prevent AD and other allergic diseases, enhanced early identification of infants at risk of AD is increasingly important.”

The detailed analysis of AD risk associated with parental atopy in early life “may help to risk stratify infants to optimize early interventions for prevention or early treatment of AD,” they wrote.

LucaLorenzelli/Thinkstock

The study was published in Pediatric Dermatology.

For the analysis, Dr. O’Connor of the department of pediatrics and child health at University College Cork (Ireland) and colleagues conducted a secondary analysis of the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study.

The study recruited 2,183 healthy first-born babies between August 2009 and October 2011 to examine the effects of environmental factors during pregnancy and infancy on childhood health and development. Skin barrier assessments were performed at birth, 2 months, 6 months, 12 months, and 24 months using a validated open chamber system to measure transepidermal water loss.

Parental atopy was self-reported at 2 months. Parents were asked at 2 months if the infant had an “itchy rash on the face or in the folds of the arms or legs,” as a screening question for AD. Experienced health care personnel used UK Working Party criteria to diagnose AD at 6, 12, and 24 months.

Complete data on AD status was available for 1,505 children in the cohort. Dr. O’Connor and colleagues calculated an overall AD prevalence of 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months.

Overall prevalence of AD was highest at 6 months. The study showed a similar or slightly higher impact of paternal atopy on offspring AD development, compared to maternal atopy.

Multivariable logistic regression analysis revealed that the odds of AD were 1.57 at 6 months and 1.66 at 12 months for maternal AD; 1.90 at 6 months and 1.85 at 24 months for paternal AD; 1.76 at 6 months and 1.75 at 12 months for maternal asthma; and 1.70 at 6 months, 1.86 at 12 months, and 1.99 at 24 months for paternal asthma.

“Parental allergic rhinitis was not associated with AD in offspring in the first 2 years, except for maternal rhinitis at 24 months [an adjusted odds ratio of 1.79],” the authors wrote. “The genetic predisposition to allergic rhinitis, given the key role of aeroallergen sensitization in its pathogenesis, may not be associated with early onset AD, but may have a greater impact in later onset or persistent AD.”

The authors acknowledged certain limitations of the study, including the fact that it was a secondary data analysis, and that parental AD, asthma, and rhinitis were self-reported, “which may reduce reliability and may contribute to the differences seen between the impact of maternal and paternal reported atopy on offspring,” they wrote. “Data on siblings were not captured, as participants in the study were first-born children. Filaggrin mutational analysis was not performed, which would have provided richer detail.”

The most comprehensive safety analysis of tralokinumab to date shows nothing unexpected in patients with atopic dermatitis (AD) treated for up to a year, according to a review published in the British Journal of Dermatology.

These findings underscore the mechanistic elegance of interleukin (IL)-13 inhibition and highlight potential advantages of flexible dosing, according to the study’s lead author, Eric Simpson, MD, MCR. Overall, the pooled analysis of safety data from five phase 2 and 3 trials shows that “blockade of a single cytokine provides excellent short- and long-term safety, which is useful for a severe chronic disease,” said Dr. Simpson, professor of dermatology at Oregon Health & Science University in Portland.

Most patients with AD require years of treatment. “So for clinicians to confidently report to patients the low rates of serious adverse events (AEs) and lack of immune suppression side-effect profile is very encouraging for both the provider and patient,” Dr. Simpson said, noting there were no new signals or concerning short-term AEs.

Tralokinumab (Adbry), an IL-13 antagonist administered subcutaneously, was approved by the Food and Drug Administration for treatment of moderate to severe AD in adults in December 2021.
 

Minor differences vs. placebo

In the pooled analysis involving 1,605 patients treated for 16 weeks with tralokinumab and 680 who received placebo, frequency of any AE was 65.7% and 67.2%, respectively. Severe AEs occurred in 4.6% and 6.3% of patients, respectively.

The most common AE overall was AD, which occurred less often in tralokinumab-treated patients (15.4%) than those on placebo (26.2%). Other common AEs that occurred more frequently with tralokinumab included viral upper respiratory tract infections (15.7% vs. 12.2%), upper respiratory tract infections (URTI, 5.6% vs. 4.8%), conjunctivitis (5.4% vs. 1.9%), and injection-site reactions (3.5% vs. 0.3%).

AEs that occurred less often with tralokinumab than placebo included skin infections (3.7% vs. 9.2%, respectively) and infected dermatitis (1.6% vs. 6.4%).

Regarding safety areas of special interest, eye disorders classified as conjunctivitis, keratoconjunctivitis, or keratitis occurred more commonly with tralokinumab (7.9%) than placebo (3.4%). Most eye disorders were mild or moderate and resolved during the study. During maintenance treatment up to 52 weeks, AE rates mirrored those in the initial treatment period and did not increase with treatment duration.

In fact, Dr. Simpson said, the low rate of AEs that are known to accompany type 2 blockade, such as conjunctivitis, do not increase but rather appear to drop with longer-term use. The fact that skin infections were reduced vs. placebo and decreased over time suggests that long-term IL-13 blockade with tralokinumab positively impacts skin infections, a well-known comorbidity in uncontrolled AD, he added.

Raj Chovatiya, MD, PhD, who was asked to comment on the study, said, “These findings provide additional data supporting the safety and tolerability of tralokinumab and support my personal real-world experience with tralokinumab as a safe and effective biologic therapy for patients with moderate to severe AD.”

Dr. Chovatiya is assistant professor, director of the Center for Eczema and Itch, and medical director of clinical trials at Northwestern University in Chicago.
 

Four-week dosing

Consistent with ECZTRA 3, the rates of URTIs and conjunctivitis were lower with maintenance dosing 300 mg every 4 weeks, consideration of which is approved for responders weighing less than 220 pounds, vs. 300 mg every 2 weeks. Specifically, 6.7% of patients on every 4-week dosing schedule experienced URTIs, vs. 9.4% on the every 2-week dosing schedule and 7% of those on the every 2-week dosing schedule plus optional topical corticosteroids. Corresponding figures for conjunctivitis were 3%, 5%, and 5.6%, respectively.

“Four-week dosing is a possibility in your patients with a good clinical response at 16 weeks,” Dr. Simpson said. Advantages include improved convenience for patients, he added, and this analysis shows that dosing every 4 weeks may improve tolerability, with a lower rate of conjunctivitis.

Although it is difficult to directly compare review data to other studies, said Dr. Chovatiya, findings also suggest that tralokinumab may be associated with reduced infections and conjunctivitis compared with other advanced AD therapies. Head-to-head trials and real-world studies are needed to better understand comparative safety, he added.

Some patients will lose a degree of response with the 4-week dosing schedule, Dr. Simpson said. In ECZTRA 1 and 2, 55.9% of patients who achieved investigator global assessment (IGA) scores of 0 or 1 after 16 weeks of dosing every 2 weeks maintained this response level through week 52, vs. 42.4% of responders who switched from dosing every 2 weeks to every 4 weeks after week 16. But according to data that Dr. Simpson recently presented, 95% of patients switched to monthly dosing who relapsed and returned to dosing every 2 weeks regained their original response level within approximately 4 weeks.

In his personal practice, Dr. Simpson has prescribed tralokinumab for patients with AD for up to a year. However, he and fellow investigators have been following much larger populations for more than 2 years and are planning additional publications. “Safety data will continue to accrue” said Dr. Simpson, “but I don’t expect any surprises.”

The clinical trials were sponsored by MedImmune (phase 2b) and LEO Pharma ( ECZTRA phase 3 trials), which also sponsored the review. Dr. Simpson reports grants and personal fees from numerous pharmaceutical companies. Dr. Chovatiya has been an advisory board member, consultant, investigator, and speaker for numerous pharmaceutical companies including LEO Pharma.

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

The most comprehensive safety analysis of tralokinumab to date shows nothing unexpected in patients with atopic dermatitis (AD) treated for up to a year, according to a review published in the British Journal of Dermatology.

These findings underscore the mechanistic elegance of interleukin (IL)-13 inhibition and highlight potential advantages of flexible dosing, according to the study’s lead author, Eric Simpson, MD, MCR. Overall, the pooled analysis of safety data from five phase 2 and 3 trials shows that “blockade of a single cytokine provides excellent short- and long-term safety, which is useful for a severe chronic disease,” said Dr. Simpson, professor of dermatology at Oregon Health & Science University in Portland.

Most patients with AD require years of treatment. “So for clinicians to confidently report to patients the low rates of serious adverse events (AEs) and lack of immune suppression side-effect profile is very encouraging for both the provider and patient,” Dr. Simpson said, noting there were no new signals or concerning short-term AEs.

Tralokinumab (Adbry), an IL-13 antagonist administered subcutaneously, was approved by the Food and Drug Administration for treatment of moderate to severe AD in adults in December 2021.
 

Minor differences vs. placebo

In the pooled analysis involving 1,605 patients treated for 16 weeks with tralokinumab and 680 who received placebo, frequency of any AE was 65.7% and 67.2%, respectively. Severe AEs occurred in 4.6% and 6.3% of patients, respectively.

The most common AE overall was AD, which occurred less often in tralokinumab-treated patients (15.4%) than those on placebo (26.2%). Other common AEs that occurred more frequently with tralokinumab included viral upper respiratory tract infections (15.7% vs. 12.2%), upper respiratory tract infections (URTI, 5.6% vs. 4.8%), conjunctivitis (5.4% vs. 1.9%), and injection-site reactions (3.5% vs. 0.3%).

AEs that occurred less often with tralokinumab than placebo included skin infections (3.7% vs. 9.2%, respectively) and infected dermatitis (1.6% vs. 6.4%).

Regarding safety areas of special interest, eye disorders classified as conjunctivitis, keratoconjunctivitis, or keratitis occurred more commonly with tralokinumab (7.9%) than placebo (3.4%). Most eye disorders were mild or moderate and resolved during the study. During maintenance treatment up to 52 weeks, AE rates mirrored those in the initial treatment period and did not increase with treatment duration.

In fact, Dr. Simpson said, the low rate of AEs that are known to accompany type 2 blockade, such as conjunctivitis, do not increase but rather appear to drop with longer-term use. The fact that skin infections were reduced vs. placebo and decreased over time suggests that long-term IL-13 blockade with tralokinumab positively impacts skin infections, a well-known comorbidity in uncontrolled AD, he added.

Raj Chovatiya, MD, PhD, who was asked to comment on the study, said, “These findings provide additional data supporting the safety and tolerability of tralokinumab and support my personal real-world experience with tralokinumab as a safe and effective biologic therapy for patients with moderate to severe AD.”

Dr. Chovatiya is assistant professor, director of the Center for Eczema and Itch, and medical director of clinical trials at Northwestern University in Chicago.
 

Four-week dosing

Consistent with ECZTRA 3, the rates of URTIs and conjunctivitis were lower with maintenance dosing 300 mg every 4 weeks, consideration of which is approved for responders weighing less than 220 pounds, vs. 300 mg every 2 weeks. Specifically, 6.7% of patients on every 4-week dosing schedule experienced URTIs, vs. 9.4% on the every 2-week dosing schedule and 7% of those on the every 2-week dosing schedule plus optional topical corticosteroids. Corresponding figures for conjunctivitis were 3%, 5%, and 5.6%, respectively.

“Four-week dosing is a possibility in your patients with a good clinical response at 16 weeks,” Dr. Simpson said. Advantages include improved convenience for patients, he added, and this analysis shows that dosing every 4 weeks may improve tolerability, with a lower rate of conjunctivitis.

Although it is difficult to directly compare review data to other studies, said Dr. Chovatiya, findings also suggest that tralokinumab may be associated with reduced infections and conjunctivitis compared with other advanced AD therapies. Head-to-head trials and real-world studies are needed to better understand comparative safety, he added.

Some patients will lose a degree of response with the 4-week dosing schedule, Dr. Simpson said. In ECZTRA 1 and 2, 55.9% of patients who achieved investigator global assessment (IGA) scores of 0 or 1 after 16 weeks of dosing every 2 weeks maintained this response level through week 52, vs. 42.4% of responders who switched from dosing every 2 weeks to every 4 weeks after week 16. But according to data that Dr. Simpson recently presented, 95% of patients switched to monthly dosing who relapsed and returned to dosing every 2 weeks regained their original response level within approximately 4 weeks.

In his personal practice, Dr. Simpson has prescribed tralokinumab for patients with AD for up to a year. However, he and fellow investigators have been following much larger populations for more than 2 years and are planning additional publications. “Safety data will continue to accrue” said Dr. Simpson, “but I don’t expect any surprises.”

The clinical trials were sponsored by MedImmune (phase 2b) and LEO Pharma ( ECZTRA phase 3 trials), which also sponsored the review. Dr. Simpson reports grants and personal fees from numerous pharmaceutical companies. Dr. Chovatiya has been an advisory board member, consultant, investigator, and speaker for numerous pharmaceutical companies including LEO Pharma.

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

The most comprehensive safety analysis of tralokinumab to date shows nothing unexpected in patients with atopic dermatitis (AD) treated for up to a year, according to a review published in the British Journal of Dermatology.

These findings underscore the mechanistic elegance of interleukin (IL)-13 inhibition and highlight potential advantages of flexible dosing, according to the study’s lead author, Eric Simpson, MD, MCR. Overall, the pooled analysis of safety data from five phase 2 and 3 trials shows that “blockade of a single cytokine provides excellent short- and long-term safety, which is useful for a severe chronic disease,” said Dr. Simpson, professor of dermatology at Oregon Health & Science University in Portland.

Most patients with AD require years of treatment. “So for clinicians to confidently report to patients the low rates of serious adverse events (AEs) and lack of immune suppression side-effect profile is very encouraging for both the provider and patient,” Dr. Simpson said, noting there were no new signals or concerning short-term AEs.

Tralokinumab (Adbry), an IL-13 antagonist administered subcutaneously, was approved by the Food and Drug Administration for treatment of moderate to severe AD in adults in December 2021.
 

Minor differences vs. placebo

In the pooled analysis involving 1,605 patients treated for 16 weeks with tralokinumab and 680 who received placebo, frequency of any AE was 65.7% and 67.2%, respectively. Severe AEs occurred in 4.6% and 6.3% of patients, respectively.

The most common AE overall was AD, which occurred less often in tralokinumab-treated patients (15.4%) than those on placebo (26.2%). Other common AEs that occurred more frequently with tralokinumab included viral upper respiratory tract infections (15.7% vs. 12.2%), upper respiratory tract infections (URTI, 5.6% vs. 4.8%), conjunctivitis (5.4% vs. 1.9%), and injection-site reactions (3.5% vs. 0.3%).

AEs that occurred less often with tralokinumab than placebo included skin infections (3.7% vs. 9.2%, respectively) and infected dermatitis (1.6% vs. 6.4%).

Regarding safety areas of special interest, eye disorders classified as conjunctivitis, keratoconjunctivitis, or keratitis occurred more commonly with tralokinumab (7.9%) than placebo (3.4%). Most eye disorders were mild or moderate and resolved during the study. During maintenance treatment up to 52 weeks, AE rates mirrored those in the initial treatment period and did not increase with treatment duration.

In fact, Dr. Simpson said, the low rate of AEs that are known to accompany type 2 blockade, such as conjunctivitis, do not increase but rather appear to drop with longer-term use. The fact that skin infections were reduced vs. placebo and decreased over time suggests that long-term IL-13 blockade with tralokinumab positively impacts skin infections, a well-known comorbidity in uncontrolled AD, he added.

Raj Chovatiya, MD, PhD, who was asked to comment on the study, said, “These findings provide additional data supporting the safety and tolerability of tralokinumab and support my personal real-world experience with tralokinumab as a safe and effective biologic therapy for patients with moderate to severe AD.”

Dr. Chovatiya is assistant professor, director of the Center for Eczema and Itch, and medical director of clinical trials at Northwestern University in Chicago.
 

Four-week dosing

Consistent with ECZTRA 3, the rates of URTIs and conjunctivitis were lower with maintenance dosing 300 mg every 4 weeks, consideration of which is approved for responders weighing less than 220 pounds, vs. 300 mg every 2 weeks. Specifically, 6.7% of patients on every 4-week dosing schedule experienced URTIs, vs. 9.4% on the every 2-week dosing schedule and 7% of those on the every 2-week dosing schedule plus optional topical corticosteroids. Corresponding figures for conjunctivitis were 3%, 5%, and 5.6%, respectively.

“Four-week dosing is a possibility in your patients with a good clinical response at 16 weeks,” Dr. Simpson said. Advantages include improved convenience for patients, he added, and this analysis shows that dosing every 4 weeks may improve tolerability, with a lower rate of conjunctivitis.

Although it is difficult to directly compare review data to other studies, said Dr. Chovatiya, findings also suggest that tralokinumab may be associated with reduced infections and conjunctivitis compared with other advanced AD therapies. Head-to-head trials and real-world studies are needed to better understand comparative safety, he added.

Some patients will lose a degree of response with the 4-week dosing schedule, Dr. Simpson said. In ECZTRA 1 and 2, 55.9% of patients who achieved investigator global assessment (IGA) scores of 0 or 1 after 16 weeks of dosing every 2 weeks maintained this response level through week 52, vs. 42.4% of responders who switched from dosing every 2 weeks to every 4 weeks after week 16. But according to data that Dr. Simpson recently presented, 95% of patients switched to monthly dosing who relapsed and returned to dosing every 2 weeks regained their original response level within approximately 4 weeks.

In his personal practice, Dr. Simpson has prescribed tralokinumab for patients with AD for up to a year. However, he and fellow investigators have been following much larger populations for more than 2 years and are planning additional publications. “Safety data will continue to accrue” said Dr. Simpson, “but I don’t expect any surprises.”

The clinical trials were sponsored by MedImmune (phase 2b) and LEO Pharma ( ECZTRA phase 3 trials), which also sponsored the review. Dr. Simpson reports grants and personal fees from numerous pharmaceutical companies. Dr. Chovatiya has been an advisory board member, consultant, investigator, and speaker for numerous pharmaceutical companies including LEO Pharma.

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

Also known as Asian or Chinese lizard’s tail (or Sam-baekcho in Korea), Saururus chinensis is an East Asian plant used in traditional medicine for various indications including edema, gonorrhea, jaundice, hypertension, leproma, pneumonia, and rheumatoid arthritis.^1,2 Specifically, Korean traditional medicine practitioners as well as Native Americans and early colonists in what is now the United States used the botanical to treat cancer, edema, rheumatoid arthritis, and other inflammatory conditions.^2-4 Modern research has produced evidence supporting the use of this plant in the dermatologic realm. This column focuses on the relevant bench science and possible applications.

Various beneficial effects

In 2008, Yoo et al. found that the ethanol extract of the dried aerial parts of S. chinensis exhibit anti-inflammatory, antiangiogenic, and antinociceptive properties, which they suggested may partially account for the established therapeutic effects of the plant.² Also, Lee et al. reported in 2012 on the antiproliferative effects against human cancer cell lines of neolignans found in S. chinensis.⁵

magicflute002 / iStock / Getty Images

Antioxidant properties have been associated with S. chinensis. In 2014, Kim et al. reported that S. chinensis extract attenuated the lipopolysaccharide (LPS)-stimulated neuroinflammatory response in BV-2 microglia cells, a result that the authors partly ascribed to the antioxidant constituents (particularly quercetin) of the plant.³
 

Atopic dermatitis

In 2008, Choi et al. determined that the leaves of S. chinensis impeded the formation of atopic dermatitis–like skin lesions in NC/Nga mice caused by repeated application of picryl chloride, potentially by stimulating the Th1 cell response, thus modulating Th1/Th2 imbalance. They concluded that S. chinensis has potential as an adjunct treatment option for atopic dermatitis.⁶

Anti-inflammatory activity

In 2010, Bae et al. studied the anti-inflammatory properties of sauchinone, a lignan derived from S. chinensis reputed to exert antioxidant, anti-inflammatory, and hepatoprotective activity,⁷ using LPS-stimulated RAW264.7 cells. They found that the lignan lowered tumor necrosis factor (TNF)–alpha synthesis by inhibiting the c-Raf-MEK1/2-ERK1/2 phosphorylation pathway, accounting for the anti-inflammatory effects of the S. chinensis constituent.⁸

More recently, Zhang et al. determined that the ethanol extract of S. chinensis leaves impaired proinflammatory gene expression by blocking the TAK1/AP-1 pathway in LPS-treated RAW264.7 macrophages. They suggested that such suppression is a significant step in the anti-inflammatory function exhibited by the plant.¹
 

Photoprotection

Park et al. investigated in 2013 the beneficial effects of sauchinone. Specifically, they studied potential photoprotective effects of the lignan against UVB in HaCaT human epidermal keratinocytes. They found that sauchinone (5-40 mcm) conferred significant protection as evaluated by cell viability and a toxicity assay. At 20-40 mcm, sauchinone blocked the upregulation of matrix metalloproteinase (MMP)–1 proteins and decrease of type 1 collagen engendered by UVB exposure. The investigators further discovered that sauchinone diminished the synthesis of reactive oxygen species. Overall, they determined that sauchinone imparted protection by suppressing extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK signaling through the activation of oxidative defense enzymes.⁷

Potential use as a depigmenting agent

In 2009, Seo et al. isolated the lignans manassantin A and B from S. chinensis and determined that these compounds dose-dependently impeded melanin synthesis in alpha-melanocyte stimulating hormone (alpha-MSH)–activated melanoma B16 cells. They also noted that manassantin A suppressed forskolin- or 3-isobutyl-1-methylxanthine (IBMX)–induced melanin production and diminished cellular levels of IBMX-inducible tyrosinase protein. The lignan had no effect on the catalytic activity of cell-free tyrosinase, an important enzyme in melanin pigment production. The researchers concluded that their results suggest the potential for S. chinensis to be used to treat hyperpigmentation disorders.⁹

Two years later Lee et al. found that manassantin A, derived from S. chinensis, steadily suppressed the cAMP elevator IBMX- or dibutyryl cAMP-induced melanin synthesis in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or the TRP1 gene. The lignan also inhibited microphthalmia-associated transcription factor (MITF) induction via the IBMX-activated cAMP-responsive element-binding protein (CREB) pathway, thus preventing the Ser-133 phosphorylation of CREB. The researchers concluded that this molecular disruption of melanin production suggests the potential for the use of manassantin A as a skin depigmenting agent.¹⁰

That same year, another S. chinensis lignan gained interest. Yun et al. investigated the effects of the S. chinensis lignan component saucerneol D on melanin synthesis in cAMP-elevated melanocytes. They found that the lignan efficiently impeded melanin product in B16 melanoma cells stimulated with alpha-MSH or other cAMP elevators. Saucerneol D was also credited with down-regulating alpha-MSH–induced gene expression of tyrosinase at the transcription level in B16 cells, suppressing alpha-MSH–induced phosphorylation of CREB in the cells, and inhibiting MITF induction. The investigators concluded that their results point to the potential of the S. chinensis lignan saucerneol D for the treatment of hyperpigmentation disorders.¹¹

In 2012, Chang et al. observed that an extract of S. chinensis and one of its constituent lignans, manassantin B, prevented melanosome transport in normal human melanocytes and Melan-a melanocytes, by interrupting the interaction between melanophilin and myosin Va. The investigators concluded that as a substance that can hinder melanosome transport, manassantin B displays potential for use as depigmenting product.¹²

The following year, Lee et al. studied the effects of S. chinensis extracts on the melanogenesis signaling pathway activated by alpha-MSH, finding dose-dependent inhibition without provoking cytotoxicity in B16F10 cells. Further, the team found evidence that the depigmenting activity exhibited by S. chinensis extracts may occur as a result of MITF and tyrosinase expression stemming from elevated activity of extracellular signal-regulated kinase (ERK). They concluded that their results support further examination of S. chinensis for its potential to contribute to skin whitening.⁵
 

Conclusion

S. chinensis has been used for many years in traditional medicine, particularly in Asia, and this interesting botanical cosmeceutical ingredient is included in Asian skin care products. Multiple lignan constituents in this plant-derived ingredient appear to yield anti-inflammatory, antioxidant, photoprotective, and antitumor properties. Its inhibitory effects on melanin production and its antiaging abilities make it worthy of further study and consideration of inclusion in antiaging skin care products.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in the office and as an e-commerce solution. Write to her at [email protected].

References

1. Zhang J et al. J Ethnopharmacol. 2021 Oct 28;279:114400.

2. Yoo HJ et al. J Ethnopharmacol. 2008 Nov 20;120(2):282-6.

3. Kim BW et al. BMC Complement Altern Med. 2014 Dec 16;14:502.

4. Lee DH et al. Biol Pharm Bull. 2013;36(5):772-9.

5. Lee YJ et al. Biol Pharm Bull. 2012;35(8):1361-6.

6. Choi MS et al. Biol Pharm Bull. 2008 Jan;31(1):51-6.

7. Park G et al. Biol Pharm Bull. 2013;36(7):1134-9.

8. Bae HB et al. Int Immunopharmacol. 2010 Sep;10(9):1022-8.

9. Seo CS et al. Phytother Res. 2009 Nov;23(11):1531-6.

10. Lee HD et al. Exp Dermatol. 2011 Sep;20(9):761-3.

11. Yun JY et al. Arch Pharm Res. 2011 Aug;34(8):1339-45.

12. Chang H et al. Pigment Cell Melanoma Res. 2012 Nov;25(6):765-72.
 

Also known as Asian or Chinese lizard’s tail (or Sam-baekcho in Korea), Saururus chinensis is an East Asian plant used in traditional medicine for various indications including edema, gonorrhea, jaundice, hypertension, leproma, pneumonia, and rheumatoid arthritis.^1,2 Specifically, Korean traditional medicine practitioners as well as Native Americans and early colonists in what is now the United States used the botanical to treat cancer, edema, rheumatoid arthritis, and other inflammatory conditions.^2-4 Modern research has produced evidence supporting the use of this plant in the dermatologic realm. This column focuses on the relevant bench science and possible applications.

Various beneficial effects

In 2008, Yoo et al. found that the ethanol extract of the dried aerial parts of S. chinensis exhibit anti-inflammatory, antiangiogenic, and antinociceptive properties, which they suggested may partially account for the established therapeutic effects of the plant.² Also, Lee et al. reported in 2012 on the antiproliferative effects against human cancer cell lines of neolignans found in S. chinensis.⁵

magicflute002 / iStock / Getty Images

Antioxidant properties have been associated with S. chinensis. In 2014, Kim et al. reported that S. chinensis extract attenuated the lipopolysaccharide (LPS)-stimulated neuroinflammatory response in BV-2 microglia cells, a result that the authors partly ascribed to the antioxidant constituents (particularly quercetin) of the plant.³
 

Atopic dermatitis

In 2008, Choi et al. determined that the leaves of S. chinensis impeded the formation of atopic dermatitis–like skin lesions in NC/Nga mice caused by repeated application of picryl chloride, potentially by stimulating the Th1 cell response, thus modulating Th1/Th2 imbalance. They concluded that S. chinensis has potential as an adjunct treatment option for atopic dermatitis.⁶

Anti-inflammatory activity

In 2010, Bae et al. studied the anti-inflammatory properties of sauchinone, a lignan derived from S. chinensis reputed to exert antioxidant, anti-inflammatory, and hepatoprotective activity,⁷ using LPS-stimulated RAW264.7 cells. They found that the lignan lowered tumor necrosis factor (TNF)–alpha synthesis by inhibiting the c-Raf-MEK1/2-ERK1/2 phosphorylation pathway, accounting for the anti-inflammatory effects of the S. chinensis constituent.⁸

More recently, Zhang et al. determined that the ethanol extract of S. chinensis leaves impaired proinflammatory gene expression by blocking the TAK1/AP-1 pathway in LPS-treated RAW264.7 macrophages. They suggested that such suppression is a significant step in the anti-inflammatory function exhibited by the plant.¹
 

Photoprotection

Park et al. investigated in 2013 the beneficial effects of sauchinone. Specifically, they studied potential photoprotective effects of the lignan against UVB in HaCaT human epidermal keratinocytes. They found that sauchinone (5-40 mcm) conferred significant protection as evaluated by cell viability and a toxicity assay. At 20-40 mcm, sauchinone blocked the upregulation of matrix metalloproteinase (MMP)–1 proteins and decrease of type 1 collagen engendered by UVB exposure. The investigators further discovered that sauchinone diminished the synthesis of reactive oxygen species. Overall, they determined that sauchinone imparted protection by suppressing extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK signaling through the activation of oxidative defense enzymes.⁷

Potential use as a depigmenting agent

In 2009, Seo et al. isolated the lignans manassantin A and B from S. chinensis and determined that these compounds dose-dependently impeded melanin synthesis in alpha-melanocyte stimulating hormone (alpha-MSH)–activated melanoma B16 cells. They also noted that manassantin A suppressed forskolin- or 3-isobutyl-1-methylxanthine (IBMX)–induced melanin production and diminished cellular levels of IBMX-inducible tyrosinase protein. The lignan had no effect on the catalytic activity of cell-free tyrosinase, an important enzyme in melanin pigment production. The researchers concluded that their results suggest the potential for S. chinensis to be used to treat hyperpigmentation disorders.⁹

Two years later Lee et al. found that manassantin A, derived from S. chinensis, steadily suppressed the cAMP elevator IBMX- or dibutyryl cAMP-induced melanin synthesis in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or the TRP1 gene. The lignan also inhibited microphthalmia-associated transcription factor (MITF) induction via the IBMX-activated cAMP-responsive element-binding protein (CREB) pathway, thus preventing the Ser-133 phosphorylation of CREB. The researchers concluded that this molecular disruption of melanin production suggests the potential for the use of manassantin A as a skin depigmenting agent.¹⁰

That same year, another S. chinensis lignan gained interest. Yun et al. investigated the effects of the S. chinensis lignan component saucerneol D on melanin synthesis in cAMP-elevated melanocytes. They found that the lignan efficiently impeded melanin product in B16 melanoma cells stimulated with alpha-MSH or other cAMP elevators. Saucerneol D was also credited with down-regulating alpha-MSH–induced gene expression of tyrosinase at the transcription level in B16 cells, suppressing alpha-MSH–induced phosphorylation of CREB in the cells, and inhibiting MITF induction. The investigators concluded that their results point to the potential of the S. chinensis lignan saucerneol D for the treatment of hyperpigmentation disorders.¹¹

In 2012, Chang et al. observed that an extract of S. chinensis and one of its constituent lignans, manassantin B, prevented melanosome transport in normal human melanocytes and Melan-a melanocytes, by interrupting the interaction between melanophilin and myosin Va. The investigators concluded that as a substance that can hinder melanosome transport, manassantin B displays potential for use as depigmenting product.¹²

The following year, Lee et al. studied the effects of S. chinensis extracts on the melanogenesis signaling pathway activated by alpha-MSH, finding dose-dependent inhibition without provoking cytotoxicity in B16F10 cells. Further, the team found evidence that the depigmenting activity exhibited by S. chinensis extracts may occur as a result of MITF and tyrosinase expression stemming from elevated activity of extracellular signal-regulated kinase (ERK). They concluded that their results support further examination of S. chinensis for its potential to contribute to skin whitening.⁵
 

Conclusion

S. chinensis has been used for many years in traditional medicine, particularly in Asia, and this interesting botanical cosmeceutical ingredient is included in Asian skin care products. Multiple lignan constituents in this plant-derived ingredient appear to yield anti-inflammatory, antioxidant, photoprotective, and antitumor properties. Its inhibitory effects on melanin production and its antiaging abilities make it worthy of further study and consideration of inclusion in antiaging skin care products.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in the office and as an e-commerce solution. Write to her at [email protected].

References

1. Zhang J et al. J Ethnopharmacol. 2021 Oct 28;279:114400.

2. Yoo HJ et al. J Ethnopharmacol. 2008 Nov 20;120(2):282-6.

3. Kim BW et al. BMC Complement Altern Med. 2014 Dec 16;14:502.

4. Lee DH et al. Biol Pharm Bull. 2013;36(5):772-9.

5. Lee YJ et al. Biol Pharm Bull. 2012;35(8):1361-6.

6. Choi MS et al. Biol Pharm Bull. 2008 Jan;31(1):51-6.

7. Park G et al. Biol Pharm Bull. 2013;36(7):1134-9.

8. Bae HB et al. Int Immunopharmacol. 2010 Sep;10(9):1022-8.

9. Seo CS et al. Phytother Res. 2009 Nov;23(11):1531-6.

10. Lee HD et al. Exp Dermatol. 2011 Sep;20(9):761-3.

11. Yun JY et al. Arch Pharm Res. 2011 Aug;34(8):1339-45.

12. Chang H et al. Pigment Cell Melanoma Res. 2012 Nov;25(6):765-72.
 

Also known as Asian or Chinese lizard’s tail (or Sam-baekcho in Korea), Saururus chinensis is an East Asian plant used in traditional medicine for various indications including edema, gonorrhea, jaundice, hypertension, leproma, pneumonia, and rheumatoid arthritis.^1,2 Specifically, Korean traditional medicine practitioners as well as Native Americans and early colonists in what is now the United States used the botanical to treat cancer, edema, rheumatoid arthritis, and other inflammatory conditions.^2-4 Modern research has produced evidence supporting the use of this plant in the dermatologic realm. This column focuses on the relevant bench science and possible applications.

Various beneficial effects

In 2008, Yoo et al. found that the ethanol extract of the dried aerial parts of S. chinensis exhibit anti-inflammatory, antiangiogenic, and antinociceptive properties, which they suggested may partially account for the established therapeutic effects of the plant.² Also, Lee et al. reported in 2012 on the antiproliferative effects against human cancer cell lines of neolignans found in S. chinensis.⁵

magicflute002 / iStock / Getty Images

Antioxidant properties have been associated with S. chinensis. In 2014, Kim et al. reported that S. chinensis extract attenuated the lipopolysaccharide (LPS)-stimulated neuroinflammatory response in BV-2 microglia cells, a result that the authors partly ascribed to the antioxidant constituents (particularly quercetin) of the plant.³
 

Atopic dermatitis

In 2008, Choi et al. determined that the leaves of S. chinensis impeded the formation of atopic dermatitis–like skin lesions in NC/Nga mice caused by repeated application of picryl chloride, potentially by stimulating the Th1 cell response, thus modulating Th1/Th2 imbalance. They concluded that S. chinensis has potential as an adjunct treatment option for atopic dermatitis.⁶

Anti-inflammatory activity

In 2010, Bae et al. studied the anti-inflammatory properties of sauchinone, a lignan derived from S. chinensis reputed to exert antioxidant, anti-inflammatory, and hepatoprotective activity,⁷ using LPS-stimulated RAW264.7 cells. They found that the lignan lowered tumor necrosis factor (TNF)–alpha synthesis by inhibiting the c-Raf-MEK1/2-ERK1/2 phosphorylation pathway, accounting for the anti-inflammatory effects of the S. chinensis constituent.⁸

More recently, Zhang et al. determined that the ethanol extract of S. chinensis leaves impaired proinflammatory gene expression by blocking the TAK1/AP-1 pathway in LPS-treated RAW264.7 macrophages. They suggested that such suppression is a significant step in the anti-inflammatory function exhibited by the plant.¹
 

Photoprotection

Park et al. investigated in 2013 the beneficial effects of sauchinone. Specifically, they studied potential photoprotective effects of the lignan against UVB in HaCaT human epidermal keratinocytes. They found that sauchinone (5-40 mcm) conferred significant protection as evaluated by cell viability and a toxicity assay. At 20-40 mcm, sauchinone blocked the upregulation of matrix metalloproteinase (MMP)–1 proteins and decrease of type 1 collagen engendered by UVB exposure. The investigators further discovered that sauchinone diminished the synthesis of reactive oxygen species. Overall, they determined that sauchinone imparted protection by suppressing extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK signaling through the activation of oxidative defense enzymes.⁷

Potential use as a depigmenting agent

In 2009, Seo et al. isolated the lignans manassantin A and B from S. chinensis and determined that these compounds dose-dependently impeded melanin synthesis in alpha-melanocyte stimulating hormone (alpha-MSH)–activated melanoma B16 cells. They also noted that manassantin A suppressed forskolin- or 3-isobutyl-1-methylxanthine (IBMX)–induced melanin production and diminished cellular levels of IBMX-inducible tyrosinase protein. The lignan had no effect on the catalytic activity of cell-free tyrosinase, an important enzyme in melanin pigment production. The researchers concluded that their results suggest the potential for S. chinensis to be used to treat hyperpigmentation disorders.⁹

Two years later Lee et al. found that manassantin A, derived from S. chinensis, steadily suppressed the cAMP elevator IBMX- or dibutyryl cAMP-induced melanin synthesis in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or the TRP1 gene. The lignan also inhibited microphthalmia-associated transcription factor (MITF) induction via the IBMX-activated cAMP-responsive element-binding protein (CREB) pathway, thus preventing the Ser-133 phosphorylation of CREB. The researchers concluded that this molecular disruption of melanin production suggests the potential for the use of manassantin A as a skin depigmenting agent.¹⁰

That same year, another S. chinensis lignan gained interest. Yun et al. investigated the effects of the S. chinensis lignan component saucerneol D on melanin synthesis in cAMP-elevated melanocytes. They found that the lignan efficiently impeded melanin product in B16 melanoma cells stimulated with alpha-MSH or other cAMP elevators. Saucerneol D was also credited with down-regulating alpha-MSH–induced gene expression of tyrosinase at the transcription level in B16 cells, suppressing alpha-MSH–induced phosphorylation of CREB in the cells, and inhibiting MITF induction. The investigators concluded that their results point to the potential of the S. chinensis lignan saucerneol D for the treatment of hyperpigmentation disorders.¹¹

In 2012, Chang et al. observed that an extract of S. chinensis and one of its constituent lignans, manassantin B, prevented melanosome transport in normal human melanocytes and Melan-a melanocytes, by interrupting the interaction between melanophilin and myosin Va. The investigators concluded that as a substance that can hinder melanosome transport, manassantin B displays potential for use as depigmenting product.¹²

The following year, Lee et al. studied the effects of S. chinensis extracts on the melanogenesis signaling pathway activated by alpha-MSH, finding dose-dependent inhibition without provoking cytotoxicity in B16F10 cells. Further, the team found evidence that the depigmenting activity exhibited by S. chinensis extracts may occur as a result of MITF and tyrosinase expression stemming from elevated activity of extracellular signal-regulated kinase (ERK). They concluded that their results support further examination of S. chinensis for its potential to contribute to skin whitening.⁵
 

Conclusion

S. chinensis has been used for many years in traditional medicine, particularly in Asia, and this interesting botanical cosmeceutical ingredient is included in Asian skin care products. Multiple lignan constituents in this plant-derived ingredient appear to yield anti-inflammatory, antioxidant, photoprotective, and antitumor properties. Its inhibitory effects on melanin production and its antiaging abilities make it worthy of further study and consideration of inclusion in antiaging skin care products.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in the office and as an e-commerce solution. Write to her at [email protected].

References

1. Zhang J et al. J Ethnopharmacol. 2021 Oct 28;279:114400.

2. Yoo HJ et al. J Ethnopharmacol. 2008 Nov 20;120(2):282-6.

3. Kim BW et al. BMC Complement Altern Med. 2014 Dec 16;14:502.

4. Lee DH et al. Biol Pharm Bull. 2013;36(5):772-9.

5. Lee YJ et al. Biol Pharm Bull. 2012;35(8):1361-6.

6. Choi MS et al. Biol Pharm Bull. 2008 Jan;31(1):51-6.

7. Park G et al. Biol Pharm Bull. 2013;36(7):1134-9.

8. Bae HB et al. Int Immunopharmacol. 2010 Sep;10(9):1022-8.

9. Seo CS et al. Phytother Res. 2009 Nov;23(11):1531-6.

10. Lee HD et al. Exp Dermatol. 2011 Sep;20(9):761-3.

11. Yun JY et al. Arch Pharm Res. 2011 Aug;34(8):1339-45.

12. Chang H et al. Pigment Cell Melanoma Res. 2012 Nov;25(6):765-72.