ECZTRA 6 Phase 3 Randomized Trial Supports Tralokinumab for Adolescent Moderate-to-Severe Atopic Dermatitis

1. Interleukin-13 targeted treatment with tralokinumab was effective and well-tolerated for adolescent moderate-to-severe atopic dermatitis.

2. No new safety signals were identified for tralokinumab moderate-to-severe atopic dermatitis treatment in adolescents, and conjunctivitis frequency did not increase throughout the treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Atopic dermatitis (AD) is characterized by recurrent pruritus and eczematous skin lesions. AD most often develops in early childhood and can impair quality of life. There are limited options for moderate to severe AD treatment in adolescents. This randomized control trial evaluated the safety profile and efficacy of interleukin (IL)-13-targeted treatment with tralokinumab monotherapy for adolescent AD. IL-13 was investigated due to its correlation to the skin barrier, immune system, and microbiome, whereas tralokinumab is a human IgG4 monoclonal antibody with a high affinity for IL-13. Of the 289 patients aged 12 to 17, 75% of the patients treated with tralokinumab saw an improvement in the Eczema Area and Severity Index (EASI) by week 16. Furthermore, more patients on tralokinumab vs the placebo had an Investigator’s Global Assessment (IGA) score of either 0 (clear) or 1 (almost clear). No new adverse reactions were reported, and conjunctivitis frequency was low. Some limitations include the small sample size, the lack of a placebo group in the maintenance phase, and potential bias from the not-blinded open-label treatment phase. Additionally, a direct comparison of tralokinumab to another targeted treatment or immunosuppressant was not evaluated.

Click to read the study in JAMA Dermatology

Relevant Reading: Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis

In-Depth [randomized control trial]: This 52-week phase 3, randomized, double-blinded, placebo-controlled study investigated the safety profile and efficacy of interleukin (IL)-13-targeted treatment with tralokinumab monotherapy for adolescent AD. This therapy was compared to a placebo. 72 centres across North America, Europe, Asia, and Australia were included in this trial. Randomization (1:1:1) was achieved through a central interactive response system, and each patient received either subcutaneous tralokinumab (i.e., 150 or 300 mg) or a placebo. After the loading dose (twice the subsequent dose) at week 0, treatment was every 2 weeks for 16 weeks. Patients that met the primary endpoint at week 16 without using any rescue mediation after week 2 were termed ‘responders.’ The responders were randomized (1:1) for maintenance treatment until week 52. For the tralokinumab group, maintenance treatment was the original dose (i.e., 150 or 300 mg) every 2 or every 4 weeks. The responders from the placebo group continued to receive a blinded placebo every 2 weeks until week 52. Non-responders were given tralokinumab open-label treatment (300 mg) every 2 weeks with optional weak-to-moderate topical corticosteroids (TCS) or calcineurin inhibitors (TCI). Inclusion criteria include a body weight ≥ 30kg, a history of AD ≥ 1 year, a history of TCS/TCI treatment, AD ≥ 10% body surface area, EASI ≥ 16 (≥12 at screening), IGA ≥ 3, and an Adolescent Worst Pruritus Numeric Rating Scale (NRS) average ≥ 4 at the week before baseline. 300 patients were randomized, and 289 comprised the analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). The primary endpoint at week 16 was an IGA score of 0 or 1 and/or an EASI 75. The secondary endpoints were an Adolescent Worst Pruritus NRS reduction of 4 or more, a change in SCORing AD, and a change in the Children’s Dermatology Life Quality Index (DLQI) from baseline to week 16. An IGA score of 0 or 1 without rescue medication at week 16 was achieved more in the 150 mg (n = 98; 21 [21.4%]) and 300 mg (n = 97; 17 [17.5%]) tralokinumab groups when compared to the placebo group (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-24.6%]; P < .001 and 13.8% [95% CI, 5.3%-22.3%]; P = .002. EASI 75, without rescue at week 16, was achieved more in the 150 mg (28 [28.6%]) and 300 mg (27 [27.8%]) tralokinumab groups when compared to the placebo group (6 [6.4%]) (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P < .001 and 22.0% [95% CI, 12.0%-32.0%]; P < .001, respectively). An Adolescent Worst Pruritus NRS reduction of 4 or more from baseline was achieved more in the 150 mg (23.2%) and 300 mg (25.0%) tralokinumab groups when compared to the placebo group (3.3%). Changing in SCORing AD and the Children’s DLQI at week 16 were greater in the 150 mg (-27.5%; -6.1%) and 300mg (-29.1%; -6.7%) tralokinumab groups when compared to the placebo group (-9.5%; -4.1%). The efficacy of tralokinumab was maintained without rescue in more than 50% of responders. At week 52, 33.3% and 57.8% of patients in the open-label phase achieved an IGA score of 0 or 1 and an EASI of 75, respectively. Lastly, tralokinumab was well tolerated with no new adverse effects. Conjunctivitis frequency did not increase through week 52. This randomized clinical trial supports tralokinumab as an effective and well-tolerated treatment for moderate-to-severe adolescent AD.

Image: PD

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