Tralokinumab improves patient-reported outcomes for atopic dermatitis
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Tralokinumab led to early and clinically meaningful improvements in patient-reported outcomes for moderate to severe atopic dermatitis compared with placebo, according to a study published in Annals of Allergy, Asthma & Immunology.
“These patient-reported outcomes include itch, sleep, quality of life and mental health,” Weily Soong, MD, chief medical officer at AllerVie Health in Birmingham, Alabama, told Healio. “This also is the first time a study has looked at [interleukin]-13 and its role in these patient-reported outcomes.”
As a fully human IgG4 monoclonal antibody, tralokinumab (Adbry, LEO Pharma) binds to the IL-13 cytokine to prevent its interaction with its receptor and subsequent downstream signaling, according to the researchers. Trials have shown it effectively treats AD alone or in combination with topical corticosteroids (TCS) through 52 weeks. In the current analysis, researchers sought to evaluate the treatment’s impact on patient-reported outcomes (PROs).
“In most atopic dermatitis trials, the primary endpoints are usually looking at the severity and the extent of the lesions,” Soong said. “However, in the real world, we definitely make clinical decisions based on quality of life, along with the severity of the lesions.”
PRO measures
The analysis comprised 1,196 patients on tralokinumab and 400 on placebo from the ECZTRA 1 and 2 trials (median age of participants, 35 years) and 253 patients on tralokinumab and TCS and 127 on placebo and TCS in the ECZTRA 3 trial (median age of participants, 36 years). About half of all patients had severe AD, with similar proportions between the treatment groups.
The researchers assessed PRO measures daily, biweekly, biweekly then monthly after 8 weeks, or monthly during the 15-week primary endpoint period.
Patients treated with tralokinumab experienced adjusted mean percentage improvements from baseline in their weekly average of worst daily pruritis numerical rating score that separated from placebo for the ECZTRA 1 and 2 participants by week 1 (difference, 5.6%; P < .001) and for the ECZTRA 3 participants by week 2 (difference, 6.2%; P < .0275).
Compared with placebo, this improvement remained greater with tralokinumab through week 16 for the ECZTRA 1 and 2 cohorts (35.3% vs. 21.3%; P < .001) and ECZTRA 3 cohort (52.4% vs. 37.4%; P < .001).
In fact, the researchers observed a separation starting on day 2 among participants assigned tralokinumab vs. placebo from ECZTRA 1 and 2 (P = .001).
“I always tell my patients that you can have really mild atopic dermatitis on your face, but it could be very itchy. It could have a high impact on anxiety and depression and on the way you look,” Soong said.
“That is the difference between just looking at the lesions versus why it’s important to look at lesions and quality of life,” he continued. “That is why quality of life has to be encompassed in your treatment decisions.”
Participants assigned tralokinumab experienced similar improvements in sleep, as their adjusted mean percentage improvement from baseline in weekly average of worst daily eczema-related sleep interference separated from those on placebo by week 1 (difference, 7.4%; P < .001) in ECZTRA 1 and 2 and by week 2 (difference, 3.7%; P < .047) for ECZTRA 3. Again, these improvements persisted through week 16 for ECZTRA 1 and 2 (39.7% vs. 18.5%; P < .001) and ECZTRA 3 (63% vs. 47%; P < .001) participants.
“You can’t sleep because itching tends to be worse at night, so you’re not sleeping very well and that just adds and compounds all your performances during the day,” Soong said. “It really decreases your school performance, your athletic performance and then, obviously as a profession, the way that you do your work every day.
“If you have trouble sleeping well, you just have a decrease in quality of life in general,” Soong added. “Then also your mental health, such as depression and anxiety, worsens.”
Researchers assessed health-related quality of life using the Dermatology Life Quality Index, which showed separations in adjusted mean percentage changes between those on tralokinumab and placebo in ECZTRA 1 and 2 by week 2 (difference, 14.3%; P < .001) and by week 6 in ECZTRA 3 (difference, 8%; P = .02), with these improvements again persisting to week 16.
Among patients with Hospital Anxiety and Depression scores of eight or higher at baseline, a greater proportion of those treated with tralokinumab vs. placebo had scores of less than 8 in both domains at week 16 in ECZTRA 1 and 2 (30.1% vs. 17.3% P < .001) and in ECZTRA 3 (53.9% vs. 29.6%; P = .003).
“If you’re itching all the time, you have these lesions, and then you [can become] very anxious about it,” Soong said. “You start making a lot of social decisions, like whether you want to go out to see people, or go out on a date, especially for an adolescent. These are all very impactful on your day-to-day activities and on your sexual activities.”
Participants in ECZTRA 3 received as-needed mometasone or topical calcineurin inhibitors. Researchers observed a steady increase in TCS use in the placebo group with separation occurring by weeks 9 and 10 (P < .05). By 15 to 16 weeks, patients on tralokinumab used about 50% less TCS (P < .002).
Also, a greater proportion of patients assigned tralokinumab vs. placebo achieved 5 to 7 TCS-free days (37.1% vs. 21.4%; P = .04), with this difference largely sustained through week 16.
“The No. 1 fear of steroid creams among patients is the side effects. Over time, you get skin atrophy and thinning of the skin,” Soong said. “The other thing is the constant daily application of creams. It takes a significant part of their day, and that adds to the decrease in quality of life.”
These constant applications also lead to anxiety and depression, Soong continued, while the expensive costs of these creams can be frustrating for patients as well.
The researchers further noted the comparable safety profiles between tralokinumab and placebo, with most adverse events categorized as mild or moderate in severity across the entire study population.
Next steps
Overall, the researchers said they were encouraged by the results.
“I was very happy to see improvements within 2 weeks, and then the sustainability of the improvement in the quality of their lives over 52 weeks,” Soong said.
“The other thing that I was very happy to see was that this does show that blocking IL-13 does have an impact on itching. And if it improves itching, it will improve all these other quality-of-life measures,” he continued.
Soong encouraged doctors to discuss options with their patients.
“I call this the golden age of atopic dermatitis treatment. We now have multiple treatment options to treat moderate to severe atopic dermatitis,” Soong said.
“You can now specifically ask patients, ‘What are our exact treatment goals? What makes you happy in your therapy? Is it the decreasing of lesions, decreasing of itching, or is it the administration of the drug and the way it’s being administered?’ ” he added. “You can look at other quality-of-life aspects, so we can specifically ask patients, ‘What is your goal in the treatment of atopic dermatitis? Let’s work on trying to reach that goal.’”