Tralokinumab (Adbry): How It Works, Clinical Evidence, and What to Expect

What Is Tralokinumab and How Does It Work?

Tralokinumab is a fully human IgG4 monoclonal antibody that binds interleukin-13 with high affinity, preventing it from interacting with its type II receptor complex. IL-13 is a dominant driver of type 2 inflammation in atopic dermatitis, directly contributing to impaired skin barrier function, itch signaling, and epidermal thickening.

Unlike broader immunosuppressants such as cyclosporine or systemic corticosteroids, tralokinumab targets a single cytokine. This selective approach leaves IL-4 signaling through its type I receptor intact, which may explain differences in side-effect profiles compared to agents that block both IL-4 and IL-13 1. The specificity matters because IL-13 alone is sufficient to reproduce many of the hallmark changes seen in atopic dermatitis skin, including reduced filaggrin expression and increased periostin production 2.

The FDA approved tralokinumab-ldrm (Adbry) in December 2021 based on three phase 3 trials: ECZTRA 1, ECZTRA 2, and ECZTRA 3 3. It is indicated for adults whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

ECZTRA 1 and ECZTRA 2: Monotherapy Trial Results

Both ECZTRA 1 (N=802) and ECZTRA 2 (N=794) were randomized, double-blind, placebo-controlled trials that evaluated tralokinumab 300 mg every two weeks as monotherapy for 16 weeks, followed by a maintenance phase extending to 52 weeks 4.

The co-primary endpoints were achieving IGA 0 or 1 (clear or almost clear skin) and EASI-75 (75% or greater improvement in the Eczema Area and Severity Index) at week 16. Results were statistically significant across both studies. In ECZTRA 1, 15.8% of tralokinumab patients achieved IGA 0/1 versus 7.1% on placebo (P=0.002), and 25.0% reached EASI-75 versus 12.7% on placebo (P<0.001). ECZTRA 2 showed similar separation: 22.2% IGA 0/1 versus 10.9% placebo (P<0.001), and 33.2% EASI-75 versus 11.4% placebo (P<0.001) 4.

Itch reduction was also measured. Pruritus NRS scores improved by 4 or more points in a significantly larger proportion of tralokinumab patients compared to placebo. By week 52, responders who continued tralokinumab every two weeks maintained their IGA 0/1 response at rates of 51.3% (ECZTRA 1) and 59.3% (ECZTRA 2), showing durable efficacy 4.

A dose-spacing analysis within these trials is also worth noting. Patients who responded at 16 weeks were re-randomized to tralokinumab every two weeks, every four weeks, or placebo. Those receiving the every-four-week regimen maintained responses at lower rates than those on the every-two-week schedule, suggesting that biweekly dosing is the more reliable maintenance strategy for most patients.

ECZTRA 3: Combination With Topical Corticosteroids

ECZTRA 3 (N=380) tested tralokinumab combined with topical corticosteroids (TCS) as needed, reflecting a more typical real-world treatment pattern 5. At 16 weeks, 38.9% of patients on tralokinumab plus TCS achieved EASI-75 compared to 26.2% on placebo plus TCS (P=0.004).

The combination approach also reduced the total amount of topical corticosteroid used. Patients on tralokinumab used fewer grams of TCS per week, which is clinically relevant given the side effects of long-term steroid use on thinning skin. The 32-week data confirmed sustained responses, with 89.6% of week-16 EASI-75 responders maintaining that response through week 32 on continued tralokinumab every two weeks 5.

Dr. Eric Simpson, professor of dermatology at Oregon Health & Science University and a principal investigator for ECZTRA 3, noted: "The steroid-sparing effect observed in the combination arm is meaningful for patients managing chronic disease where prolonged topical steroid use raises concerns about skin atrophy and adrenal suppression" 5.

How to Use Tralokinumab: Dosing and Administration

The recommended dosing regimen starts with a loading dose of 600 mg on day 1, administered as four separate 150 mg subcutaneous injections. After the loading dose, patients inject 300 mg (two prefilled syringes) every other week 3.

Injection sites include the thigh, abdomen (avoiding the 5 cm area around the navel), and upper arm (if administered by a caregiver). Rotate sites with each dose. Allow the prefilled syringe to reach room temperature for 30 minutes before injecting. Do not shake the syringe.

Patients should receive age-appropriate immunizations before initiating tralokinumab. Live vaccines can be administered during treatment, as tralokinumab does not broadly suppress adaptive immunity, but clinicians should consult current guidelines 3. No dose adjustment is required for renal or hepatic impairment. The drug has not been studied in pregnant women, and it should be used during pregnancy only if the potential benefit justifies the potential risk.

Side Effects and Safety Profile

Across the ECZTRA trials, the most common adverse events with tralokinumab were upper respiratory tract infections (23.4% vs 20.5% placebo), conjunctivitis (7.5% vs 3.2% placebo), and injection site reactions (7.2% vs 4.4% placebo) 4.

Conjunctivitis rates deserve specific attention. While lower than those reported with dupilumab in its registration trials (where rates ranged from 8.6% to 22.1% depending on the study), conjunctivitis still occurred more frequently with tralokinumab than placebo 6. Most cases were mild to moderate and resolved without discontinuation. Patients with a history of conjunctivitis or keratitis should discuss baseline eye health with their prescriber before starting treatment.

Serious adverse events occurred at similar rates between tralokinumab and placebo groups. Eczema herpeticum, a concern with immunomodulators in atopic dermatitis, was rare (<1%) and not significantly different from placebo 4. No cases of anaphylaxis were reported in the key trials.

Long-term safety data from the open-label ECZTEND trial (following patients for up to 4.5 years of continuous treatment) confirmed no new safety signals and showed sustained efficacy with continued use 7.

Tralokinumab vs. Dupilumab: How Do They Compare?

Both tralokinumab and dupilumab (Dupixent) are injectable biologics for moderate-to-severe atopic dermatitis. The primary mechanistic difference: dupilumab blocks both IL-4 and IL-13 by targeting the shared IL-4 receptor alpha subunit, while tralokinumab neutralizes IL-13 alone 8.

No head-to-head trial has been published. Cross-trial comparisons suggest dupilumab achieves numerically higher IGA 0/1 and EASI-75 rates in its monotherapy studies (SOLO 1 and SOLO 2 showed EASI-75 rates of 44%, 51% at 16 weeks) compared to tralokinumab's 25%, 33% range 6. These comparisons have significant limitations, including different patient populations, disease severity at baseline, and trial designs.

Dupilumab also carries FDA approvals for asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and COPD with type 2 inflammation, whereas tralokinumab is currently approved only for atopic dermatitis in adults 3. For patients who have tried dupilumab without adequate response, or who experience intolerable side effects (particularly conjunctivitis), tralokinumab offers a mechanistically distinct alternative.

According to the American Academy of Dermatology's 2024 guidelines for atopic dermatitis management: "Biologic agents targeting type 2 cytokines, including dupilumab and tralokinumab, are recommended for adults with moderate-to-severe disease who are candidates for systemic therapy" 9.

How Tralokinumab Differs From Topical Retinoids

Some patients researching skin treatments encounter both biologics like tralokinumab and topical retinoids such as tretinoin (Retin-A), adapalene (Differin), tazarotene (Tazorac), or trifarotene (Aklief). These treat entirely different conditions through unrelated mechanisms.

Topical retinoids are vitamin A derivatives that normalize keratinocyte differentiation and are primarily prescribed for acne vulgaris and photoaging 10. Tretinoin remains the gold standard for photoaging, with over 35 years of clinical evidence supporting its efficacy in reducing fine wrinkles and hyperpigmentation. Adapalene, now available over the counter at 0.1%, is the most tolerable retinoid option for acne-prone skin. Tazarotene is the most potent topical retinoid for both acne and psoriasis. Trifarotene (Aklief) is the newest, with selective RAR-gamma activity that allows treatment of truncal acne 11.

Tralokinumab would never replace a retinoid, and vice versa. Patients with atopic dermatitis should generally avoid retinoids on actively inflamed skin, as the irritation they cause can worsen dermatitis flares. A patient using tralokinumab for eczema might separately use a retinoid on non-affected facial skin for acne or anti-aging purposes, but this requires coordination with a dermatologist to manage irritation thresholds.

Cost, Insurance Coverage, and Patient Support

Tralokinumab's wholesale acquisition cost is approximately $3,250 per month for the maintenance regimen 3. Most commercial insurers cover it with prior authorization, though step therapy requirements are common. Many plans require documented failure of at least one systemic immunosuppressant or dupilumab before approving tralokinumab.

The manufacturer offers a copay assistance program that can reduce out-of-pocket costs to as low as $0 per month for eligible commercially insured patients. Patients with Medicare or Medicaid are not eligible for the copay program but may access the drug through specialty pharmacy benefit managers or patient assistance foundations.

Prior authorization typically requires documentation of disease severity (IGA score of 3 or 4, or BSA involvement above 10%), failure of topical therapies, and for some plans, failure of at least one prior biologic. The approval process usually takes 5 to 15 business days, though peer-to-peer reviews can extend timelines.

Who Is a Candidate for Tralokinumab?

Adults with moderate-to-severe atopic dermatitis who have not responded adequately to topical corticosteroids and calcineurin inhibitors are potential candidates. The drug is not approved for children, though pediatric trials are ongoing.

Good candidates typically present with widespread disease (BSA above 10%), significant itch that disrupts sleep or daily activities, and a history of topical treatment failure. Patients who prefer a targeted mechanism that does not suppress IL-4 signaling may favor tralokinumab over dupilumab, particularly if they have concerns about conjunctivitis risk or have experienced IL-4-related side effects on dupilumab.

Tralokinumab is not appropriate for acute skin infections, isolated contact dermatitis, or mild eczema manageable with emollients and low-potency steroids. Before prescribing, clinicians should confirm the atopic dermatitis diagnosis and rule out mimickers such as cutaneous T-cell lymphoma, allergic contact dermatitis, or scabies.

Patients initiating tralokinumab should expect to evaluate efficacy at 16 weeks, consistent with the primary endpoint timeline used in the ECZTRA trials 4. If IGA has not improved by at least one grade and EASI has not decreased by 50% or more at that time point, reassessment of the treatment plan is warranted.