Tralokinumab Effectively Treats Moderate-to-Severe Atopic Dermatitis: Real-World Data

Coco Dekkers, PhD candidate

Credit: LinkedIn

A study showed tralokinumab is an effective treatment for moderate-to-severe atopic dermatitis in adult patients who are both dupilumab-naïve and dupilumab non-naïve.¹

“This prospective multicenter study provides insight into the daily practice effectiveness and safety of the first 28 weeks of treatment with tralokinumab in adult [atopic dermatitis] patients,” wrote investigators, led by Coco Dekkers, PhD candidate, from University Medical Center Utrecht in the Netherlands.

Tralokinumab, a biological that targets interleukin-13, is a relatively new advanced systemic treatment for patients with moderate-to-severe atopic dermatitis.² Phase 3 trials demonstrated the efficacy and safety of this drug, but more daily practice data was needed.

Investigators sought to evaluate the 28-week safety and effectiveness of tralokinumab in daily practice, as well as serum proteins and total IgE levels, in patients with atopic dermatitis.¹ The team collected data from patients from the BioDay registry, including a total of 84 patients with 39 dupilumab-naïve and 45 who had previously failed dupilumab treatment. The sample had a mean age of 42.5 years with 48.8% male.

Among the sample, 8 patients (9.5%) were actively treated with concomitant systemic immunosuppressive treatments, often cyclosporine, and 32 patients (38.1%) were in the washout of previous systemic immunosuppressive treatment. The sample included 26.2% patients who started tralokinumab during the washout period of dupilumab.

The primary endpoints were the absolute values of the Eczema Area and Severity Index (EASI) (range: 0 – 72), Numeric Rating Scale for pruritus (0 – 10), Numeric Rating Scale for pain, Dermatology Life Quality Index (0 – 30), and Patient-Oriented Eczema Measure (0 – 28) after 4, 16, and 28 weeks of treatment with tralokinumab. Investigators chose to examine absolute values over relative values since earlier systemic therapies did influence data after weeks 16 and 28. Secondary endpoints included absolute cutoff scores of EASI ≤ 7, IGA ≤ 1, and Numeric Rating Scale for pruritus ≤ 4 after 4, 16, and 28 weeks of treatment.

At baseline, participants had a mean EASI of 11.0; the average for dupilumab-naïve and non-naïve patients was 12.2 and 9.8, respectively. Additionally, patients exposed to dupilumab (62.2%) had a greater recorded use of concomitant immunosuppressive treatment than dupilumab-naïve patients (30.8%). The IGA significantly differed among patients who were and were not naïve to dupilumab, with moderate-to-severe disease found in most dupilumab-naïve patients and mild-to-moderate disease found in non-naïve patients.

The study showed all primary outcomes significantly improved during the follow-up period. By week 28, the mean EASI reduced from 11.0 (95% confidence interval [CI], 9.1 – 12.8) to 4.9 (95% CI, 4.0 – 5.8), and the Numeric Rating Scale for pruritus reduced from 6.1 (95% CI, 5.5 – 6.7) to 4.6 (95% CI, 4.0 – 5.2).

Despite finding the change in EASI and Numeric Rating Scale for pruritus significantly differed between dupilumab-naïve and dupilumab non-naïve patients during treatment, the groups had small absolute differences after 28 weeks (EASI: 4.7 vs 5.3; Numeric Rating Scale for pruritus: 4.3 vs 4.8, respectively).

Investigators observed a similar trend when comparing patients with complete washout (n = 44) vs without complete washout (n = 40) of other immunosuppressive therapies at the beginning of tralokinumab treatment. Patients without complete washout had a lower EASI at baseline and a lower percentage of improvement in EASI from baseline compared with patients with a complete washout.

The study discovered the probability of achieving EASI ≤ 7, Numeric Rating Scale for pruritus ≤ 4, and IGA ≤ 1 after 28 weeks of treatment was 75.8%. Participants who were dupilumab-naïve vs non-naïve had a greater likelihood of achieving these endpoints.

Patients (n = 46) reported 62 adverse events during 28 weeks of treatment. Most adverse events were mild (58.1%), and common ones included eye disorders (28.6%), general disorders such as malaise (9.5%), nervous system disorders such as headaches (9.5%), and skin and subcutaneous disorders such as hair loss (9.5%).

In total, 13 patients (15.5%) discontinued treatment following an adverse event. All 6 patients who experienced hair loss discontinued the treatment. Other adverse events leading to discontinuation included conjunctivitis (n = 5), headache (n = 1), and rosacea (n = 1).

Among 10 patients who were previously treated with dupilumab an average of 20 weeks before starting tralokinumab treatment, the serum concentration of dupilumab after the 10-week washout period reached maximum values of 0.052 mg/L. Moreover, the median serum IgE level significantly decreased on average from 1096.0 to 671.0 in dupilumab-naïve patients and 360.0 to 331.0 in dupilumab non-naïve patients after 28 weeks of treatment from baseline.

“Despite acting on the same immunologic pathway, our study indicates that considering tralokinumab after dupilumab discontinuation is a valuable option,” investigators concluded.

References

1. ^{Dekkers C, Zuithoff N, Bakker D, Knol E, Wevers A, Touwslager W, Christoffers W, Prosje P, van Lynden-van Nes A, van Lümig P, Kamsteeg M, Oosting AJ, Schuttelaar MLA, Haeck I, de Graaf M, van Wijk F, de Bruin-Weller M. Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28-Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels. Allergy. 2024 Dec 14. doi: 10.1111/all.16414. Epub ahead of print. PMID: 39673366.}
2. ^{Blair HA. Tralokinumab in Atopic Dermatitis: A Profile of Its Use. Clin Drug Investig. 2022 Apr;42(4):365-374. doi: 10.1007/s40261-022-01135-9. Epub 2022 Mar 22. PMID: 35316850.}