The efficacy and safety of tralokinumab plus topical corticosteroids (TCS) for the treatment of severe atopic dermatitis (AD) in adults with inadequate response or intolerance to cyclosporine A found support in study data published in the British Journal of Dermatology.
This double-blind placebo-controlled phase 3 trial enrolled adults with severe AD from dermatology centers in Europe. Eligible patients had experienced inadequate response or intolerance to systemic treatment with cyclosporine A. Patients who did not receive treatment with cyclosporine A due to contraindications were also enrolled.
Patients were randomly assigned 1:1 to receive 26 weeks of subcutaneous tralokinumab 300 mg every 2 weeks plus TCS as needed or subcutaneous placebo every 2 weeks plus TCS as needed. At week 26, patients were invited to enter a long-term extension study. The primary endpoint was Eczema Area Severity Index (EASI) at week 16. Secondary endpoints included 75% improvement on EASI from baseline (EASI75) and 90% improvement on EASI from baseline (EASI90). Safety events were monitored throughout the trial duration.
From December 2018 to September 2020, a total of 277 patients were randomly assigned: 140 to tralokinumab and 137 to placebo. Demographic characteristics were comparable between study arms. Median age was 34.0 years; 59.6% were men; and 98.2% were White. Median AD duration was 26.0 years; median body surface area involvement was 52.0%. Overall, 74.7% patients had previous CSA exposure; the most common reasons for discontinuation were inadequate efficacy (34.3%) and adverse events (31.0%). Among the 25.3% of patients with no previous CSA use, the primary reasons were contraindications (18.8%) and risk for adverse events (3.2%). Nearly all patients (99.6%) had previous exposure to topical corticosteroids.
At week 16, the percentage of patients achieving EASI75 was significantly greater in the tralokinumab plus TCS group compared with the placebo plus TCS group (64.2% vs 50.5%; P =.018). At week 26, this gap widened to 68.8% vs 55.3% (P =.014). EASI90 was also more prevalent in the tralokinumab group vs placebo at week 16 (41.1% vs 29.3%; P =.032) and week 26 (48.6% vs 36.4%; P =.027). At weeks 16 and 26, the tralokinumab group displayed greater reductions in mean pruritus scores and greater improvements on the Dermatology Life Quality Index compared with placebo. Treatment response rates were similar between patients with previous failed cyclosporine A therapy and patients with no exposure to cyclosporine A.
The frequency of adverse events was comparable between groups. In all, 77.5% of patients in the tralokinumab group and 78.8% in the placebo group reported adverse events. The majority of adverse events were mild or moderate in severity, with most resolving by the end of treatment. The most frequent adverse event was viral upper respiratory tract infection, accounting for 12.2% of all reports. A serious adverse event was reported with tralokinumab but was not considered related to treatment. There were 9 serious adverse events reported in the placebo group. Conjunctivitis occurred more frequently with tralokinumab vs placebo (9.4% vs 4.4%), although all cases resolved by treatment conclusion and none resulted in discontinuation of tralokinumab.
Results from this trial identify tralokinumab plus topical corticosteroids as a valid treatment option for patients with inadequate response to cyclosporine A, the investigators posited, who also suggest that patients with intolerance to certain systemic treatments may also benefit from tralokinumab.
“The ECZTRA 7 trial supports the efficacy and safety of tralokinumab plus TCS as needed in adult European patients with severe AD, who were not adequately controlled with or had contraindications to oral CSA,” investigators wrote. “These results are consistent with those observed in [prior] tralokinumab trials and support the use of tralokinumab plus TCS as a therapy in patients with severe refractory AD.”
Disclosure: This research was sponsored by LEO Pharma A/S. Please see the original reference for a full list of disclosures
Gutermuth J, Pink AE, Worm M, Soldbro L, Bjerregård Øland C, Weidinger S. Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of cyclosporine A: a placebo-controlled, randomized, Phase 3 clinical trial (ECZTRA 7). Br J Dermatol. Published online October 26, 2021. doi:10.1111/bjd.20832