Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), baricitinib with or without topical corticosteroids (TCS) resulted in rapid achievement of the recommended absolute Eczema Area and Severity Index (EASI) and SCORing of AD (SCORAD) outcomes, which were sustained until week 16.

Major finding: An EASI score of ≤7 and a SCORAD score of <25 were achieved by significantly more patients receiving baricitinib (2 or 4 mg) vs placebo at all timepoints from week 1 (all P ≤ .01 and all P ≤ .05, respectively) and those receiving 4 mg baricitinib + TCS vs placebo + TCS at all timepoints from week 2 (all P ≤ .05 for both).

Study details: This post hoc analysis included 1316 patients with moderate-to-severe AD who received baricitinib (2 or 4 mg) or placebo in BREEZE-AD1/AD2 or baricitinib (2 or 4 mg)+TCS or placebo+TCS in BREEZE-AD7 for 16 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Three authors declared being current or former employees or shareholders of Eli Lilly.

Source: Thyssen JP et al. Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. J Dermatolog Treat. 2023;34(1):2216322 (Jun 21). Doi: 10.1080/09546634.2023.2216322

Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), baricitinib with or without topical corticosteroids (TCS) resulted in rapid achievement of the recommended absolute Eczema Area and Severity Index (EASI) and SCORing of AD (SCORAD) outcomes, which were sustained until week 16.

Major finding: An EASI score of ≤7 and a SCORAD score of <25 were achieved by significantly more patients receiving baricitinib (2 or 4 mg) vs placebo at all timepoints from week 1 (all P ≤ .01 and all P ≤ .05, respectively) and those receiving 4 mg baricitinib + TCS vs placebo + TCS at all timepoints from week 2 (all P ≤ .05 for both).

Study details: This post hoc analysis included 1316 patients with moderate-to-severe AD who received baricitinib (2 or 4 mg) or placebo in BREEZE-AD1/AD2 or baricitinib (2 or 4 mg)+TCS or placebo+TCS in BREEZE-AD7 for 16 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Three authors declared being current or former employees or shareholders of Eli Lilly.

Source: Thyssen JP et al. Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. J Dermatolog Treat. 2023;34(1):2216322 (Jun 21). Doi: 10.1080/09546634.2023.2216322

Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), baricitinib with or without topical corticosteroids (TCS) resulted in rapid achievement of the recommended absolute Eczema Area and Severity Index (EASI) and SCORing of AD (SCORAD) outcomes, which were sustained until week 16.

Major finding: An EASI score of ≤7 and a SCORAD score of <25 were achieved by significantly more patients receiving baricitinib (2 or 4 mg) vs placebo at all timepoints from week 1 (all P ≤ .01 and all P ≤ .05, respectively) and those receiving 4 mg baricitinib + TCS vs placebo + TCS at all timepoints from week 2 (all P ≤ .05 for both).

Study details: This post hoc analysis included 1316 patients with moderate-to-severe AD who received baricitinib (2 or 4 mg) or placebo in BREEZE-AD1/AD2 or baricitinib (2 or 4 mg)+TCS or placebo+TCS in BREEZE-AD7 for 16 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Three authors declared being current or former employees or shareholders of Eli Lilly.

Source: Thyssen JP et al. Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. J Dermatolog Treat. 2023;34(1):2216322 (Jun 21). Doi: 10.1080/09546634.2023.2216322

Key clinical point: Upadacitinib demonstrated an acceptable safety profile and led to significant and sustained improvements in disease signs and symptoms through 48 weeks of observation in patients with moderate-to-severe atopic dermatitis (AD) who were unresponsive to conventional treatments.

Major finding: At weeks 16 and 48, an Eczema Area and Severity Index-75 response was achieved by 78.2% and 87.6% of patients, respectively, with a significant reduction in mean sleeplessness, skin pain, and itch Numeric Rating Scale scores (all P < .001). Most adverse events were of mild-to-moderate severity.

Study details: This real-world prospective study included 146 adult patients with moderate-to-severe AD who were unresponsive, intolerant, or had contraindications to the approved therapies for moderate-to-severe AD and received 15 or 30 mg upadacitinib alone or combined with corticosteroids for 48 weeks.

Disclosures: This study did not receive any funding. Some authors, including the lead author, declared serving as investigators, speakers, advisory board members, or consultants for or receiving lecture or speaker honoraria, research grants, or personal fees from various sources.

Source: Chiricozzi A et al. Long-term effectiveness and safety of upadacitinib for atopic dermatitis in a real-world setting: An interim analysis through 48 weeks of observation. Am J Clin Dermatol. 2023 (Jun 15). Doi: 10.1007/s40257-023-00798-0

Key clinical point: Upadacitinib demonstrated an acceptable safety profile and led to significant and sustained improvements in disease signs and symptoms through 48 weeks of observation in patients with moderate-to-severe atopic dermatitis (AD) who were unresponsive to conventional treatments.

Major finding: At weeks 16 and 48, an Eczema Area and Severity Index-75 response was achieved by 78.2% and 87.6% of patients, respectively, with a significant reduction in mean sleeplessness, skin pain, and itch Numeric Rating Scale scores (all P < .001). Most adverse events were of mild-to-moderate severity.

Study details: This real-world prospective study included 146 adult patients with moderate-to-severe AD who were unresponsive, intolerant, or had contraindications to the approved therapies for moderate-to-severe AD and received 15 or 30 mg upadacitinib alone or combined with corticosteroids for 48 weeks.

Disclosures: This study did not receive any funding. Some authors, including the lead author, declared serving as investigators, speakers, advisory board members, or consultants for or receiving lecture or speaker honoraria, research grants, or personal fees from various sources.

Source: Chiricozzi A et al. Long-term effectiveness and safety of upadacitinib for atopic dermatitis in a real-world setting: An interim analysis through 48 weeks of observation. Am J Clin Dermatol. 2023 (Jun 15). Doi: 10.1007/s40257-023-00798-0

Key clinical point: Upadacitinib demonstrated an acceptable safety profile and led to significant and sustained improvements in disease signs and symptoms through 48 weeks of observation in patients with moderate-to-severe atopic dermatitis (AD) who were unresponsive to conventional treatments.

Major finding: At weeks 16 and 48, an Eczema Area and Severity Index-75 response was achieved by 78.2% and 87.6% of patients, respectively, with a significant reduction in mean sleeplessness, skin pain, and itch Numeric Rating Scale scores (all P < .001). Most adverse events were of mild-to-moderate severity.

Study details: This real-world prospective study included 146 adult patients with moderate-to-severe AD who were unresponsive, intolerant, or had contraindications to the approved therapies for moderate-to-severe AD and received 15 or 30 mg upadacitinib alone or combined with corticosteroids for 48 weeks.

Disclosures: This study did not receive any funding. Some authors, including the lead author, declared serving as investigators, speakers, advisory board members, or consultants for or receiving lecture or speaker honoraria, research grants, or personal fees from various sources.

Source: Chiricozzi A et al. Long-term effectiveness and safety of upadacitinib for atopic dermatitis in a real-world setting: An interim analysis through 48 weeks of observation. Am J Clin Dermatol. 2023 (Jun 15). Doi: 10.1007/s40257-023-00798-0

Key clinical point: Dupilumab rapidly reduced the skin abundance of Staphylococcus aureus in patients with moderate-to-severe atopic dermatitis (AD), and the reduction correlated with improvements in all AD severity measurements except itch.

Major finding: At day 3, the dupilumab vs placebo group showed a 7.5-fold reduction (P = .02) in the skin abundance of S. aureus. A significant positive correlation was observed between the reduction in abundance and SCORing Atopic Dermatitis score with dupilumab (repeated measure correlation coefficient 0.39; P < .001), which was similar for other AD severity measurements except pruritus Numeric Rating Scale score.

Study details: Findings are from the multicenter, double-blind ADRN09 trial including 71 adult patients with moderate-to-severe AD who were randomly assigned to receive dupilumab (n = 45) or placebo (n = 26).

Disclosures: This study was supported by the US National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, Colorado. Some authors declared serving as consultants or investigators for and receiving research grants from various organizations.

Source: Simpson EL et al. Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment. J Allergy Clin Immunol. 2023 (Jun 12). Doi: 10.1016/j.jaci.2023.05.026

Key clinical point: Dupilumab rapidly reduced the skin abundance of Staphylococcus aureus in patients with moderate-to-severe atopic dermatitis (AD), and the reduction correlated with improvements in all AD severity measurements except itch.

Major finding: At day 3, the dupilumab vs placebo group showed a 7.5-fold reduction (P = .02) in the skin abundance of S. aureus. A significant positive correlation was observed between the reduction in abundance and SCORing Atopic Dermatitis score with dupilumab (repeated measure correlation coefficient 0.39; P < .001), which was similar for other AD severity measurements except pruritus Numeric Rating Scale score.

Study details: Findings are from the multicenter, double-blind ADRN09 trial including 71 adult patients with moderate-to-severe AD who were randomly assigned to receive dupilumab (n = 45) or placebo (n = 26).

Disclosures: This study was supported by the US National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, Colorado. Some authors declared serving as consultants or investigators for and receiving research grants from various organizations.

Source: Simpson EL et al. Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment. J Allergy Clin Immunol. 2023 (Jun 12). Doi: 10.1016/j.jaci.2023.05.026

Key clinical point: Dupilumab rapidly reduced the skin abundance of Staphylococcus aureus in patients with moderate-to-severe atopic dermatitis (AD), and the reduction correlated with improvements in all AD severity measurements except itch.

Major finding: At day 3, the dupilumab vs placebo group showed a 7.5-fold reduction (P = .02) in the skin abundance of S. aureus. A significant positive correlation was observed between the reduction in abundance and SCORing Atopic Dermatitis score with dupilumab (repeated measure correlation coefficient 0.39; P < .001), which was similar for other AD severity measurements except pruritus Numeric Rating Scale score.

Study details: Findings are from the multicenter, double-blind ADRN09 trial including 71 adult patients with moderate-to-severe AD who were randomly assigned to receive dupilumab (n = 45) or placebo (n = 26).

Disclosures: This study was supported by the US National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, Colorado. Some authors declared serving as consultants or investigators for and receiving research grants from various organizations.

Source: Simpson EL et al. Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment. J Allergy Clin Immunol. 2023 (Jun 12). Doi: 10.1016/j.jaci.2023.05.026

Key clinical point: Atopic dermatitis (AD) is not associated with an overall increased risk for malignancy in children and adults; however, the risk for lymphoma is significantly higher in both children and adults with severe AD.

Major finding: The risk for overall malignancy was similar between the AD and non-AD groups of children (adjusted hazard ratio [aHR] 1.02; 95% CI 0.92-1.12) and adults (aHR 1.00; 95% CI 0.99-1.02); however, the risk for lymphoma (non-cutaneous T-cell type) was significantly higher in children (aHR 3.18; 95% CI 1.41-7.16) and adults (aHR 1.95; 95% CI 1.62-2.36) with severe AD.

Study details: This population-based cohort study included matched children (<18 years) with (n = 409,431) and without (n = 1,809,029) AD and matched adults with (n = 625,083) and without (n = 2,678,888) AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving research grants, consulting fees, or honoraria from Pfizer, Inc., and others. AR Lemeshow declared being an employee of Pfizer, Inc.

Source: Wan J et al. Malignancy risk in patients with atopic dermatitis: A population-based cohort study. Br J Dermatol. 2023;189(1):53-61 (Jul 7). Doi: 10.1093/bjd/ljad072

Key clinical point: Atopic dermatitis (AD) is not associated with an overall increased risk for malignancy in children and adults; however, the risk for lymphoma is significantly higher in both children and adults with severe AD.

Major finding: The risk for overall malignancy was similar between the AD and non-AD groups of children (adjusted hazard ratio [aHR] 1.02; 95% CI 0.92-1.12) and adults (aHR 1.00; 95% CI 0.99-1.02); however, the risk for lymphoma (non-cutaneous T-cell type) was significantly higher in children (aHR 3.18; 95% CI 1.41-7.16) and adults (aHR 1.95; 95% CI 1.62-2.36) with severe AD.

Study details: This population-based cohort study included matched children (<18 years) with (n = 409,431) and without (n = 1,809,029) AD and matched adults with (n = 625,083) and without (n = 2,678,888) AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving research grants, consulting fees, or honoraria from Pfizer, Inc., and others. AR Lemeshow declared being an employee of Pfizer, Inc.

Source: Wan J et al. Malignancy risk in patients with atopic dermatitis: A population-based cohort study. Br J Dermatol. 2023;189(1):53-61 (Jul 7). Doi: 10.1093/bjd/ljad072

Key clinical point: Atopic dermatitis (AD) is not associated with an overall increased risk for malignancy in children and adults; however, the risk for lymphoma is significantly higher in both children and adults with severe AD.

Major finding: The risk for overall malignancy was similar between the AD and non-AD groups of children (adjusted hazard ratio [aHR] 1.02; 95% CI 0.92-1.12) and adults (aHR 1.00; 95% CI 0.99-1.02); however, the risk for lymphoma (non-cutaneous T-cell type) was significantly higher in children (aHR 3.18; 95% CI 1.41-7.16) and adults (aHR 1.95; 95% CI 1.62-2.36) with severe AD.

Study details: This population-based cohort study included matched children (<18 years) with (n = 409,431) and without (n = 1,809,029) AD and matched adults with (n = 625,083) and without (n = 2,678,888) AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving research grants, consulting fees, or honoraria from Pfizer, Inc., and others. AR Lemeshow declared being an employee of Pfizer, Inc.

Source: Wan J et al. Malignancy risk in patients with atopic dermatitis: A population-based cohort study. Br J Dermatol. 2023;189(1):53-61 (Jul 7). Doi: 10.1093/bjd/ljad072

Key clinical point: Lebrikizumab demonstrated long-term efficacy and a safety profile consistent with that observed in previous trials in adolescents with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, 62.6% and 81.9% of patients achieved an Investigator’s Global Assessment score of 0 or 1 with a ≥2-point reduction from baseline and an Eczema Area and Severity Index-75 response, respectively. Adverse events were mostly mild or moderate in severity and led to treatment discontinuation in 2.4% of patients.

Study details: This open-label phase 3 trial, ADore, included 206 adolescents (age ≥12 to <18 years) with moderate-to-severe AD who received lebrikizumab subcutaneously (500-mg loading dose at baseline and week 2, followed by 250 mg every 2 weeks).

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors declared receiving research grants or consulting, advisory board, or speaker honoraria from or serving as consultants, speakers, or investigators for Eli Lilly and others. Six authors declared being former or current employees or shareholders of Eli Lilly.

Source: Paller AS et al. Safety and efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: A 52-week, open-label, phase 3 study. Dermatol Ther (Heidelb). 2023;13(7):1517-1534 (Jun 15). Doi: 10.1007/s13555-023-00942-y

Key clinical point: Lebrikizumab demonstrated long-term efficacy and a safety profile consistent with that observed in previous trials in adolescents with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, 62.6% and 81.9% of patients achieved an Investigator’s Global Assessment score of 0 or 1 with a ≥2-point reduction from baseline and an Eczema Area and Severity Index-75 response, respectively. Adverse events were mostly mild or moderate in severity and led to treatment discontinuation in 2.4% of patients.

Study details: This open-label phase 3 trial, ADore, included 206 adolescents (age ≥12 to <18 years) with moderate-to-severe AD who received lebrikizumab subcutaneously (500-mg loading dose at baseline and week 2, followed by 250 mg every 2 weeks).

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors declared receiving research grants or consulting, advisory board, or speaker honoraria from or serving as consultants, speakers, or investigators for Eli Lilly and others. Six authors declared being former or current employees or shareholders of Eli Lilly.

Source: Paller AS et al. Safety and efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: A 52-week, open-label, phase 3 study. Dermatol Ther (Heidelb). 2023;13(7):1517-1534 (Jun 15). Doi: 10.1007/s13555-023-00942-y

Key clinical point: Lebrikizumab demonstrated long-term efficacy and a safety profile consistent with that observed in previous trials in adolescents with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, 62.6% and 81.9% of patients achieved an Investigator’s Global Assessment score of 0 or 1 with a ≥2-point reduction from baseline and an Eczema Area and Severity Index-75 response, respectively. Adverse events were mostly mild or moderate in severity and led to treatment discontinuation in 2.4% of patients.

Study details: This open-label phase 3 trial, ADore, included 206 adolescents (age ≥12 to <18 years) with moderate-to-severe AD who received lebrikizumab subcutaneously (500-mg loading dose at baseline and week 2, followed by 250 mg every 2 weeks).

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors declared receiving research grants or consulting, advisory board, or speaker honoraria from or serving as consultants, speakers, or investigators for Eli Lilly and others. Six authors declared being former or current employees or shareholders of Eli Lilly.

Source: Paller AS et al. Safety and efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: A 52-week, open-label, phase 3 study. Dermatol Ther (Heidelb). 2023;13(7):1517-1534 (Jun 15). Doi: 10.1007/s13555-023-00942-y

Key clinical point: Long-term abrocitinib monotherapy or with medicated topical therapy demonstrates a manageable safety profile and significantly improves the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 48, in the 200 and 100 mg abrocitinib groups, Eczema Area and Severity Index-75 (EASI 75) responses and ≥4-point improvements in Peak Pruritus Numerical Rating Scale (PP-NRS) scores were achieved by 81.7% and 66.8% (EASI 75), and 67.9% and 51.1% (PP-NRS) of patients, respectively; serious treatment-emergent adverse event rates were 7.1% and 4.7% (200 mg vs 100 mg), respectively.

Study details: This phase 3 long-term extension study JADE EXTEND (n = 1116) included patients (≥12 years) with moderate-to-severe AD who completed abrocitinib (200/100 mg) or placebo treatment in JADE MONO-1, JADE MONO-2, or JADE COMPARE study and received abrocitinib (200/100 mg) with or without topical therapy.

Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants, fees, etc., from and serving as consultants, speakers, advisors, or investigators for Pfizer Inc. and others. Five authors declared being employees or shareholders of Pfizer Inc.

Source: Reich K et al. Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study. J Eur Acad Dermatol Venereol. 2023 (Jun 19). Doi: 10.1111/jdv.19280

Key clinical point: Long-term abrocitinib monotherapy or with medicated topical therapy demonstrates a manageable safety profile and significantly improves the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 48, in the 200 and 100 mg abrocitinib groups, Eczema Area and Severity Index-75 (EASI 75) responses and ≥4-point improvements in Peak Pruritus Numerical Rating Scale (PP-NRS) scores were achieved by 81.7% and 66.8% (EASI 75), and 67.9% and 51.1% (PP-NRS) of patients, respectively; serious treatment-emergent adverse event rates were 7.1% and 4.7% (200 mg vs 100 mg), respectively.

Study details: This phase 3 long-term extension study JADE EXTEND (n = 1116) included patients (≥12 years) with moderate-to-severe AD who completed abrocitinib (200/100 mg) or placebo treatment in JADE MONO-1, JADE MONO-2, or JADE COMPARE study and received abrocitinib (200/100 mg) with or without topical therapy.

Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants, fees, etc., from and serving as consultants, speakers, advisors, or investigators for Pfizer Inc. and others. Five authors declared being employees or shareholders of Pfizer Inc.

Source: Reich K et al. Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study. J Eur Acad Dermatol Venereol. 2023 (Jun 19). Doi: 10.1111/jdv.19280

Key clinical point: Long-term abrocitinib monotherapy or with medicated topical therapy demonstrates a manageable safety profile and significantly improves the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 48, in the 200 and 100 mg abrocitinib groups, Eczema Area and Severity Index-75 (EASI 75) responses and ≥4-point improvements in Peak Pruritus Numerical Rating Scale (PP-NRS) scores were achieved by 81.7% and 66.8% (EASI 75), and 67.9% and 51.1% (PP-NRS) of patients, respectively; serious treatment-emergent adverse event rates were 7.1% and 4.7% (200 mg vs 100 mg), respectively.

Study details: This phase 3 long-term extension study JADE EXTEND (n = 1116) included patients (≥12 years) with moderate-to-severe AD who completed abrocitinib (200/100 mg) or placebo treatment in JADE MONO-1, JADE MONO-2, or JADE COMPARE study and received abrocitinib (200/100 mg) with or without topical therapy.

Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants, fees, etc., from and serving as consultants, speakers, advisors, or investigators for Pfizer Inc. and others. Five authors declared being employees or shareholders of Pfizer Inc.

Source: Reich K et al. Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study. J Eur Acad Dermatol Venereol. 2023 (Jun 19). Doi: 10.1111/jdv.19280

TOPLINE:

Registry data show a lower incidence of postcolonoscopy colorectal cancer (PCCRC) among endoscopists with higher sessile serrated lesion detection rates, validating the SSLDR as a clinically relevant quality measure.

METHODOLOGY:

• An analysis of the association between PCCRC and SSLDR was conducted using data from the New Hampshire Colonoscopy Registry.
• The cohort included patients who had either a colonoscopy or a diagnosis of CRC.
• The outcome was PCCRC (that is, CRC diagnosed at least 6 months after index colonoscopy).
• The exposure of interest was endoscopist-specific SSLDR.

TAKEAWAY:

• Of 26,901 patients, 162 were diagnosed with PCCRC.
• Endoscopists with a higher SSLDR had lower unadjusted risks for PCCRC (0.3% among those with an SSLDR of at least 6.0% (hazard ratio, 0.29).
• There was a significant 14% reduction in PCCRC for each 1% increase in SSLDR (HR, 0.86).
• Roughly one-third of endoscopists had an adequate adenoma detection rate yet had an SSLDR that was less than the most protective SSLDR of 6%.

IN PRACTICE:

“Endoscopists should strive to achieve the highest SSLDR rate, perhaps with the use of artificial intelligence,” the authors wrote. “Our data linking low SSLDR to increased PCCRC support development of recommendations to measure SDR [serrated detection rates] in clinical practice, and development of educational platforms, techniques and devices to improve low SDR.”

SOURCE:

The study was led by Joseph C. Anderson, MD, with the Geisel School of Medicine at Dartmouth, Hanover, N.H. It was published online in the American Journal of Gastroenterology. The study had no commercial funding.

LIMITATIONS:

The study population came from New Hampshire, which lacks racial diversity. There may be differences in serrated polyp detection in other populations with more high-risk groups, such as smokers. There may be significant variation in SSLDR because of variation in pathological interpretation.

DISCLOSURES:

The authors reported no relevant financial conflicts of interest.

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

TOPLINE:

Registry data show a lower incidence of postcolonoscopy colorectal cancer (PCCRC) among endoscopists with higher sessile serrated lesion detection rates, validating the SSLDR as a clinically relevant quality measure.

METHODOLOGY:

• An analysis of the association between PCCRC and SSLDR was conducted using data from the New Hampshire Colonoscopy Registry.
• The cohort included patients who had either a colonoscopy or a diagnosis of CRC.
• The outcome was PCCRC (that is, CRC diagnosed at least 6 months after index colonoscopy).
• The exposure of interest was endoscopist-specific SSLDR.

TAKEAWAY:

• Of 26,901 patients, 162 were diagnosed with PCCRC.
• Endoscopists with a higher SSLDR had lower unadjusted risks for PCCRC (0.3% among those with an SSLDR of at least 6.0% (hazard ratio, 0.29).
• There was a significant 14% reduction in PCCRC for each 1% increase in SSLDR (HR, 0.86).
• Roughly one-third of endoscopists had an adequate adenoma detection rate yet had an SSLDR that was less than the most protective SSLDR of 6%.

IN PRACTICE:

“Endoscopists should strive to achieve the highest SSLDR rate, perhaps with the use of artificial intelligence,” the authors wrote. “Our data linking low SSLDR to increased PCCRC support development of recommendations to measure SDR [serrated detection rates] in clinical practice, and development of educational platforms, techniques and devices to improve low SDR.”

SOURCE:

The study was led by Joseph C. Anderson, MD, with the Geisel School of Medicine at Dartmouth, Hanover, N.H. It was published online in the American Journal of Gastroenterology. The study had no commercial funding.

LIMITATIONS:

The study population came from New Hampshire, which lacks racial diversity. There may be differences in serrated polyp detection in other populations with more high-risk groups, such as smokers. There may be significant variation in SSLDR because of variation in pathological interpretation.

DISCLOSURES:

The authors reported no relevant financial conflicts of interest.

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

TOPLINE:

Registry data show a lower incidence of postcolonoscopy colorectal cancer (PCCRC) among endoscopists with higher sessile serrated lesion detection rates, validating the SSLDR as a clinically relevant quality measure.

METHODOLOGY:

• An analysis of the association between PCCRC and SSLDR was conducted using data from the New Hampshire Colonoscopy Registry.
• The cohort included patients who had either a colonoscopy or a diagnosis of CRC.
• The outcome was PCCRC (that is, CRC diagnosed at least 6 months after index colonoscopy).
• The exposure of interest was endoscopist-specific SSLDR.

TAKEAWAY:

• Of 26,901 patients, 162 were diagnosed with PCCRC.
• Endoscopists with a higher SSLDR had lower unadjusted risks for PCCRC (0.3% among those with an SSLDR of at least 6.0% (hazard ratio, 0.29).
• There was a significant 14% reduction in PCCRC for each 1% increase in SSLDR (HR, 0.86).
• Roughly one-third of endoscopists had an adequate adenoma detection rate yet had an SSLDR that was less than the most protective SSLDR of 6%.

IN PRACTICE:

“Endoscopists should strive to achieve the highest SSLDR rate, perhaps with the use of artificial intelligence,” the authors wrote. “Our data linking low SSLDR to increased PCCRC support development of recommendations to measure SDR [serrated detection rates] in clinical practice, and development of educational platforms, techniques and devices to improve low SDR.”

SOURCE:

The study was led by Joseph C. Anderson, MD, with the Geisel School of Medicine at Dartmouth, Hanover, N.H. It was published online in the American Journal of Gastroenterology. The study had no commercial funding.

LIMITATIONS:

The study population came from New Hampshire, which lacks racial diversity. There may be differences in serrated polyp detection in other populations with more high-risk groups, such as smokers. There may be significant variation in SSLDR because of variation in pathological interpretation.

DISCLOSURES:

The authors reported no relevant financial conflicts of interest.

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

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Children and adults with attention-deficit/hyperactivity disorder (ADHD) show greater improvement in symptoms with viloxazine extended release (ER) compared with treatment with atomoxetine, new research suggests.

Investigators studied patients who started out taking atomoxetine and, after a washout period, initiated treatment with viloxazine. Participants’ ADHD symptoms were assessed prior to initiation of each treatment and after 4 weeks.

Children and adults showed significantly larger improvement in inattentiveness and hyperactivity/impulsivity when taking viloxazine vs. atomoxetine, with almost all patients preferring the former to the latter, according to results of the study.

In addition, close to one half of the study participants were taking a prior stimulant, and 85% were able to taper off stimulant treatment. Viloxazine’s effects were more rapid than were those of atomoxetine.

“It is timely to have a rapidly acting, and highly effective nonstimulant option across the full spectrum of ADHD symptoms, for both children and adults, in light of recent stimulant shortages and the new [Food and Drug Administration] boxed warnings regarding increased mortality associated with overuse of stimulants” study investigator Maxwell Z. Price, a medical student at Hackensack Meridian School of Medicine, Nutley, N.J., said in an interview.
 

Nonstimulant treatment options

Study coauthor Richard L. Price, MD, noted that the study was conducted to find a more acceptable alternative to psychostimulant treatments for ADHD, which are currently considered the “gold standard.”

Although they are effective, said Dr. Price, they are fraught with adverse effects, including appetite suppression, insomnia, exacerbation of mood disorders, anxiety, tics, or misuse.

Atomoxetine, a nonstimulant option, has been around for a few decades and is often used in combination with a stimulant medication. However, he said, the drug has a mild effect, requires frequent dosage adjustment, takes a long time to work, and people have “soured” on its utility, Dr. Price added.

Like atomoxetine, viloxazine is a selective norepinephrine inhibitor that has been used an antidepressant in Europe for 30 years. It was recently reformulated as an extended-release medication and approved by the FDA for pediatric and adult ADHD.

However, unlike atomoxetine, viloxazine is associated with increased prefrontal cortex 5-hydroxytrytamine, norepinephrine, and dopamine levels in vivo.

There have been no head-to-head trials comparing the two agents. However, even in head-to-head ADHD medication trials, the agents that are under investigation are typically compared in matched patients. The current investigators wanted to compare the two agents in the same patients whose insurers mandate a trial of generic atomoxetine prior to covering branded viloxazine.

“We wanted to find out whether patients taking atomoxetine for ADHD combined type would experience improvement in ADHD symptoms following voluntary, open-label switch to viloxazine,” said Dr. Price.

The researchers studied 50 patients who presented with ADHD combined type and had no other psychiatric, medical, or substance-related comorbidities or prior exposure to atomoxetine or viloxazine.

The study included 35 children (mean age, 11.9 ± 2.9 years; 94.3% male) and 15 adults (mean age, 29.3 ± 9.0 years; 73.3% male). Of these, 42.9% and 73.3%, respectively, were taking concurrent stimulants.

Patients received mean doses of atomoxetine once daily followed by viloxazine once daily after a 5-day washout period between the two drugs. Participants were seen weekly for titration and monitoring.

At baseline, the pediatric ADHD–Rating Scale 5 (ADHD-RS-5) and the Adult Investigator Symptoms Rating Scale (AISRS) were completed, then again after 4 weeks of treatment with atomoxetine (or upon earlier response or discontinuation due to side effects, whichever came first), and 5 days after discontinuing atomoxetine, which “reestablished the baseline score.” The same protocol was then repeated with viloxazine.
 

‘Paradigm shift’

At baseline, the total ADHD-RS-5 mean score was 40.3 ± 10.3. Improvements at 4 weeks were greater in viloxazine vs atomoxetine, with scores of 13.9 ± 10.2 vs 33.1 ± 12.1, respectively (t = -10.12, P < .00001). In inattention and hyperactivity/impulsivity, the t values were –8.57 and –9.87, respectively (both P values < .0001).

Similarly, from the baseline total, AISRS mean score of 37.3 ± 11.8, improvements were greater on viloxazine vs. atomoxetine, with scores of 11.9 ± 9.4 vs. 28.8 ± 14.9, respectively (t = −4.18, P = .0009 overall; for inattention, t = −3.50, P > .004 and for hyperactivity/impulsivity, t = 3.90, P > .002).

By 2 weeks, 86% of patients taking viloxazine reported a positive response vs. 14% when taking atomoxetine.

Side effects were lower in viloxazine vs. atomoxetine, with 36% of patients discontinuing treatment with atomoxetine because of side effects that included gastrointestinal upset, irritability, fatigue, and insomnia vs. 4% who discontinued viloxazine because of fatigue.

Almost all participants (96%) preferred viloxazine over atomoxetine and 85% were able to taper off stimulant treatment following stabilization on viloxazine.

“These were not small differences,” said Dr. Richard L. Price. “These were clinically and statistically meaningful differences.”

The findings could represent “a paradigm shift for the field” because “we always think of starting ADHD treatment with stimulants, but perhaps treatment with viloxazine could help patients to avoid stimulants entirely,” he suggested.
 

Real-world study

Commenting for this article, Greg Mattingly, MD, associate clinical professor, Washington University, St. Louis, called it “a timely addition to the clinical literature where for the first time ever we have two nonstimulant options approved for adults with ADHD.”

This real-world clinic study “yields many answers,” said Dr. Mattingly, president-elect of the American Professional Society of ADHD and Related Disorders (APSARD), who was not involved with the study.

“Simply put, this real-world study of 50 clinic patients found that viloxazine ER had faster onset, was significantly more effective, and was preferred by 96% of patients as compared to atomoxetine,” he said.

“Another intriguing part of the study that will be of high interest to both patients and providers was that, of those initially treated concurrently with stimulant and viloxazine ER, 85% were able to discontinue their stimulant medication,” Dr. Mattingly added.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The open access fee was funded by the investigators. Dr. Maxwell Z. Price certifies that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Dr. Richard L. Price has received honoraria from AbbVie, Alkermes, Idorsia, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Dr. Mattingly reports financial disclosures with various pharmaceutical companies, which are listed in full in the paper.

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

Children and adults with attention-deficit/hyperactivity disorder (ADHD) show greater improvement in symptoms with viloxazine extended release (ER) compared with treatment with atomoxetine, new research suggests.

Investigators studied patients who started out taking atomoxetine and, after a washout period, initiated treatment with viloxazine. Participants’ ADHD symptoms were assessed prior to initiation of each treatment and after 4 weeks.

Children and adults showed significantly larger improvement in inattentiveness and hyperactivity/impulsivity when taking viloxazine vs. atomoxetine, with almost all patients preferring the former to the latter, according to results of the study.

In addition, close to one half of the study participants were taking a prior stimulant, and 85% were able to taper off stimulant treatment. Viloxazine’s effects were more rapid than were those of atomoxetine.

“It is timely to have a rapidly acting, and highly effective nonstimulant option across the full spectrum of ADHD symptoms, for both children and adults, in light of recent stimulant shortages and the new [Food and Drug Administration] boxed warnings regarding increased mortality associated with overuse of stimulants” study investigator Maxwell Z. Price, a medical student at Hackensack Meridian School of Medicine, Nutley, N.J., said in an interview.
 

Nonstimulant treatment options

Study coauthor Richard L. Price, MD, noted that the study was conducted to find a more acceptable alternative to psychostimulant treatments for ADHD, which are currently considered the “gold standard.”

Although they are effective, said Dr. Price, they are fraught with adverse effects, including appetite suppression, insomnia, exacerbation of mood disorders, anxiety, tics, or misuse.

Atomoxetine, a nonstimulant option, has been around for a few decades and is often used in combination with a stimulant medication. However, he said, the drug has a mild effect, requires frequent dosage adjustment, takes a long time to work, and people have “soured” on its utility, Dr. Price added.

Like atomoxetine, viloxazine is a selective norepinephrine inhibitor that has been used an antidepressant in Europe for 30 years. It was recently reformulated as an extended-release medication and approved by the FDA for pediatric and adult ADHD.

However, unlike atomoxetine, viloxazine is associated with increased prefrontal cortex 5-hydroxytrytamine, norepinephrine, and dopamine levels in vivo.

There have been no head-to-head trials comparing the two agents. However, even in head-to-head ADHD medication trials, the agents that are under investigation are typically compared in matched patients. The current investigators wanted to compare the two agents in the same patients whose insurers mandate a trial of generic atomoxetine prior to covering branded viloxazine.

“We wanted to find out whether patients taking atomoxetine for ADHD combined type would experience improvement in ADHD symptoms following voluntary, open-label switch to viloxazine,” said Dr. Price.

The researchers studied 50 patients who presented with ADHD combined type and had no other psychiatric, medical, or substance-related comorbidities or prior exposure to atomoxetine or viloxazine.

The study included 35 children (mean age, 11.9 ± 2.9 years; 94.3% male) and 15 adults (mean age, 29.3 ± 9.0 years; 73.3% male). Of these, 42.9% and 73.3%, respectively, were taking concurrent stimulants.

Patients received mean doses of atomoxetine once daily followed by viloxazine once daily after a 5-day washout period between the two drugs. Participants were seen weekly for titration and monitoring.

At baseline, the pediatric ADHD–Rating Scale 5 (ADHD-RS-5) and the Adult Investigator Symptoms Rating Scale (AISRS) were completed, then again after 4 weeks of treatment with atomoxetine (or upon earlier response or discontinuation due to side effects, whichever came first), and 5 days after discontinuing atomoxetine, which “reestablished the baseline score.” The same protocol was then repeated with viloxazine.
 

‘Paradigm shift’

At baseline, the total ADHD-RS-5 mean score was 40.3 ± 10.3. Improvements at 4 weeks were greater in viloxazine vs atomoxetine, with scores of 13.9 ± 10.2 vs 33.1 ± 12.1, respectively (t = -10.12, P < .00001). In inattention and hyperactivity/impulsivity, the t values were –8.57 and –9.87, respectively (both P values < .0001).

Similarly, from the baseline total, AISRS mean score of 37.3 ± 11.8, improvements were greater on viloxazine vs. atomoxetine, with scores of 11.9 ± 9.4 vs. 28.8 ± 14.9, respectively (t = −4.18, P = .0009 overall; for inattention, t = −3.50, P > .004 and for hyperactivity/impulsivity, t = 3.90, P > .002).

By 2 weeks, 86% of patients taking viloxazine reported a positive response vs. 14% when taking atomoxetine.

Side effects were lower in viloxazine vs. atomoxetine, with 36% of patients discontinuing treatment with atomoxetine because of side effects that included gastrointestinal upset, irritability, fatigue, and insomnia vs. 4% who discontinued viloxazine because of fatigue.

Almost all participants (96%) preferred viloxazine over atomoxetine and 85% were able to taper off stimulant treatment following stabilization on viloxazine.

“These were not small differences,” said Dr. Richard L. Price. “These were clinically and statistically meaningful differences.”

The findings could represent “a paradigm shift for the field” because “we always think of starting ADHD treatment with stimulants, but perhaps treatment with viloxazine could help patients to avoid stimulants entirely,” he suggested.
 

Real-world study

Commenting for this article, Greg Mattingly, MD, associate clinical professor, Washington University, St. Louis, called it “a timely addition to the clinical literature where for the first time ever we have two nonstimulant options approved for adults with ADHD.”

This real-world clinic study “yields many answers,” said Dr. Mattingly, president-elect of the American Professional Society of ADHD and Related Disorders (APSARD), who was not involved with the study.

“Simply put, this real-world study of 50 clinic patients found that viloxazine ER had faster onset, was significantly more effective, and was preferred by 96% of patients as compared to atomoxetine,” he said.

“Another intriguing part of the study that will be of high interest to both patients and providers was that, of those initially treated concurrently with stimulant and viloxazine ER, 85% were able to discontinue their stimulant medication,” Dr. Mattingly added.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The open access fee was funded by the investigators. Dr. Maxwell Z. Price certifies that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Dr. Richard L. Price has received honoraria from AbbVie, Alkermes, Idorsia, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Dr. Mattingly reports financial disclosures with various pharmaceutical companies, which are listed in full in the paper.

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

Children and adults with attention-deficit/hyperactivity disorder (ADHD) show greater improvement in symptoms with viloxazine extended release (ER) compared with treatment with atomoxetine, new research suggests.

Investigators studied patients who started out taking atomoxetine and, after a washout period, initiated treatment with viloxazine. Participants’ ADHD symptoms were assessed prior to initiation of each treatment and after 4 weeks.

Children and adults showed significantly larger improvement in inattentiveness and hyperactivity/impulsivity when taking viloxazine vs. atomoxetine, with almost all patients preferring the former to the latter, according to results of the study.

In addition, close to one half of the study participants were taking a prior stimulant, and 85% were able to taper off stimulant treatment. Viloxazine’s effects were more rapid than were those of atomoxetine.

“It is timely to have a rapidly acting, and highly effective nonstimulant option across the full spectrum of ADHD symptoms, for both children and adults, in light of recent stimulant shortages and the new [Food and Drug Administration] boxed warnings regarding increased mortality associated with overuse of stimulants” study investigator Maxwell Z. Price, a medical student at Hackensack Meridian School of Medicine, Nutley, N.J., said in an interview.
 

Nonstimulant treatment options

Study coauthor Richard L. Price, MD, noted that the study was conducted to find a more acceptable alternative to psychostimulant treatments for ADHD, which are currently considered the “gold standard.”

Although they are effective, said Dr. Price, they are fraught with adverse effects, including appetite suppression, insomnia, exacerbation of mood disorders, anxiety, tics, or misuse.

Atomoxetine, a nonstimulant option, has been around for a few decades and is often used in combination with a stimulant medication. However, he said, the drug has a mild effect, requires frequent dosage adjustment, takes a long time to work, and people have “soured” on its utility, Dr. Price added.

Like atomoxetine, viloxazine is a selective norepinephrine inhibitor that has been used an antidepressant in Europe for 30 years. It was recently reformulated as an extended-release medication and approved by the FDA for pediatric and adult ADHD.

However, unlike atomoxetine, viloxazine is associated with increased prefrontal cortex 5-hydroxytrytamine, norepinephrine, and dopamine levels in vivo.

There have been no head-to-head trials comparing the two agents. However, even in head-to-head ADHD medication trials, the agents that are under investigation are typically compared in matched patients. The current investigators wanted to compare the two agents in the same patients whose insurers mandate a trial of generic atomoxetine prior to covering branded viloxazine.

“We wanted to find out whether patients taking atomoxetine for ADHD combined type would experience improvement in ADHD symptoms following voluntary, open-label switch to viloxazine,” said Dr. Price.

The researchers studied 50 patients who presented with ADHD combined type and had no other psychiatric, medical, or substance-related comorbidities or prior exposure to atomoxetine or viloxazine.

The study included 35 children (mean age, 11.9 ± 2.9 years; 94.3% male) and 15 adults (mean age, 29.3 ± 9.0 years; 73.3% male). Of these, 42.9% and 73.3%, respectively, were taking concurrent stimulants.

Patients received mean doses of atomoxetine once daily followed by viloxazine once daily after a 5-day washout period between the two drugs. Participants were seen weekly for titration and monitoring.

At baseline, the pediatric ADHD–Rating Scale 5 (ADHD-RS-5) and the Adult Investigator Symptoms Rating Scale (AISRS) were completed, then again after 4 weeks of treatment with atomoxetine (or upon earlier response or discontinuation due to side effects, whichever came first), and 5 days after discontinuing atomoxetine, which “reestablished the baseline score.” The same protocol was then repeated with viloxazine.
 

‘Paradigm shift’

At baseline, the total ADHD-RS-5 mean score was 40.3 ± 10.3. Improvements at 4 weeks were greater in viloxazine vs atomoxetine, with scores of 13.9 ± 10.2 vs 33.1 ± 12.1, respectively (t = -10.12, P < .00001). In inattention and hyperactivity/impulsivity, the t values were –8.57 and –9.87, respectively (both P values < .0001).

Similarly, from the baseline total, AISRS mean score of 37.3 ± 11.8, improvements were greater on viloxazine vs. atomoxetine, with scores of 11.9 ± 9.4 vs. 28.8 ± 14.9, respectively (t = −4.18, P = .0009 overall; for inattention, t = −3.50, P > .004 and for hyperactivity/impulsivity, t = 3.90, P > .002).

By 2 weeks, 86% of patients taking viloxazine reported a positive response vs. 14% when taking atomoxetine.

Side effects were lower in viloxazine vs. atomoxetine, with 36% of patients discontinuing treatment with atomoxetine because of side effects that included gastrointestinal upset, irritability, fatigue, and insomnia vs. 4% who discontinued viloxazine because of fatigue.

Almost all participants (96%) preferred viloxazine over atomoxetine and 85% were able to taper off stimulant treatment following stabilization on viloxazine.

“These were not small differences,” said Dr. Richard L. Price. “These were clinically and statistically meaningful differences.”

The findings could represent “a paradigm shift for the field” because “we always think of starting ADHD treatment with stimulants, but perhaps treatment with viloxazine could help patients to avoid stimulants entirely,” he suggested.
 

Real-world study

Commenting for this article, Greg Mattingly, MD, associate clinical professor, Washington University, St. Louis, called it “a timely addition to the clinical literature where for the first time ever we have two nonstimulant options approved for adults with ADHD.”

This real-world clinic study “yields many answers,” said Dr. Mattingly, president-elect of the American Professional Society of ADHD and Related Disorders (APSARD), who was not involved with the study.

“Simply put, this real-world study of 50 clinic patients found that viloxazine ER had faster onset, was significantly more effective, and was preferred by 96% of patients as compared to atomoxetine,” he said.

“Another intriguing part of the study that will be of high interest to both patients and providers was that, of those initially treated concurrently with stimulant and viloxazine ER, 85% were able to discontinue their stimulant medication,” Dr. Mattingly added.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The open access fee was funded by the investigators. Dr. Maxwell Z. Price certifies that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Dr. Richard L. Price has received honoraria from AbbVie, Alkermes, Idorsia, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Dr. Mattingly reports financial disclosures with various pharmaceutical companies, which are listed in full in the paper.

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

On July 21, 2023, topical cantharidin became the first Food and Drug Administration–approved treatment of molluscum contagiosum (molluscum), for adults and pediatric patients 2 years of age and older.

The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.

The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).

A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.

The product will be marketed as Ycanth.

In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.

On July 21, 2023, topical cantharidin became the first Food and Drug Administration–approved treatment of molluscum contagiosum (molluscum), for adults and pediatric patients 2 years of age and older.

The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.

The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).

A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.

The product will be marketed as Ycanth.

In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.

On July 21, 2023, topical cantharidin became the first Food and Drug Administration–approved treatment of molluscum contagiosum (molluscum), for adults and pediatric patients 2 years of age and older.

The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.

The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).

A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.

The product will be marketed as Ycanth.

In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.