Lebrikizumab monotherapy for AD found safe, effective during induction

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.