Adbry (Tralokinumab)
tralokinumab-ldrm · also marketed as Adtralza (EU)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Moderate-to-severe atopic dermatitis — inadequately controlled with topical therapies or when topicals not advisable | Adults (≥18 years) | Monotherapy or with TCS/TCI | FDA Approved |
| Moderate-to-severe atopic dermatitis — inadequately controlled with topical therapies or when topicals not advisable | Adolescents (≥12 years) | Monotherapy or with TCS/TCI | FDA Approved |
Tralokinumab is the first biologic to selectively target interleukin-13 (IL-13) alone, distinguishing it from dupilumab which blocks both IL-4 and IL-13 signalling. FDA approval for adults was granted in December 2021 based on the ECZTRA 1, 2, and 3 trials, with the adolescent expansion (December 2023) supported by ECZTRA 6. The drug is suitable for patients requiring systemic therapy who have failed or are not candidates for topical treatment regimens.
Moderate-to-severe asthma with eosinophilic phenotype: Tralokinumab was investigated in phase II/III asthma trials (ATMOSPHERE, MESOS, TROPOS). Results showed modest benefit in the eosinophil-high subgroup but tralokinumab did not receive regulatory approval for asthma. Evidence quality: Moderate (phase III data available, not approved).
Prurigo nodularis: Emerging case series and small observational studies suggest potential benefit. Evidence quality: Low (limited data, no RCTs).
Dosing
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Moderate-to-severe AD — initial induction | 600 mg SC (day 0) | 300 mg SC Q2W | 300 mg Q2W | Loading dose: four 150 mg PFS injections OR two 300 mg autoinjector injections Steady state reached by week 16 |
| AD responder — extended interval (adults <100 kg with clear/almost clear skin at week 16) | 600 mg SC (day 0) | 300 mg SC Q4W | 300 mg Q4W | Only for patients <100 kg achieving IGA 0/1 at week 16 Response maintenance may be lower with Q4W vs Q2W |
| AD — concomitant with topical corticosteroids | 600 mg SC (day 0) | 300 mg SC Q2W | 300 mg Q2W | TCS as needed; TCI reserved for face, neck, intertriginous areas ECZTRA 3 design |
Adolescent Dosing (12–17 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Moderate-to-severe AD — adolescent induction | 300 mg SC (day 0) | 150 mg SC Q2W | 150 mg Q2W | Loading: two 150 mg PFS injections; maintenance: one 150 mg PFS injection Administer under adult supervision; autoinjector not approved for adolescents |
Tralokinumab exposure decreases with rising body weight. In patients above 100 kg on Q4W dosing, median AUC is approximately 1.46-fold lower than in patients below 100 kg. For this reason, the Q4W extended dosing option is restricted to adult responders weighing under 100 kg (FDA PI). Consider maintaining Q2W dosing in heavier patients even if response criteria are met.
If a dose is missed, administer as soon as possible. Then resume the regular schedule from the next planned injection date (FDA PI).
Pharmacology
Mechanism of Action
Tralokinumab is a fully human IgG4 monoclonal antibody that binds with high affinity to interleukin-13 (IL-13), a central effector cytokine in Type 2 inflammation. By engaging the IL-13 molecule itself, tralokinumab prevents it from interacting with both the IL-13Rα1/IL-4Rα signalling complex and the IL-13Rα2 decoy receptor. This dual blockade suppresses downstream proinflammatory cascades driven by IL-13, including chemokine release (CCL17/TARC, CCL18, CCL26), IgE production, epidermal barrier disruption, and fibroblast-mediated collagen deposition. Clinically, IL-13 neutralisation reduces keratinocyte hyperproliferation (decreased Ki-67 and keratin 16) and restores barrier protein expression (increased loricrin), corresponding to improvements in skin inflammation, pruritus, and barrier integrity.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~76% (SC); Tmax 5–8 days; steady state by week 16 with loading dose | Slow SC absorption typical for mAbs; loading dose accelerates attainment of therapeutic levels |
| Distribution | Vd ~4.2 L; 1326 amino acids; MW ~147 kDa | Small Vd indicates largely confined to plasma/extracellular space, consistent with large-molecule biology |
| Metabolism | Proteolytic catabolism to small peptides and amino acids; no CYP involvement | No hepatic CYP-mediated interactions; confirmed no clinically significant effect on CYP1A2, 2C9, 2C19, 2D6, or 3A4 substrates |
| Elimination | t½ = 22 days; CL = 0.149 L/day; non-saturable proteolytic pathway | Long half-life supports Q2W or Q4W dosing intervals; clearance increases with body weight |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory tract infections | 23.8% (monotherapy); 30.0% (+TCS) | Includes URTI, viral URTI, pharyngitis, and nasopharyngitis; mostly reported as common cold; compare to 20.4% placebo (monotherapy) and 15.4% placebo (+TCS) |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Conjunctivitis (including allergic) | 7.5% (monotherapy); 13.6% (+TCS) | 29 events/100 subject-years; majority resolved during treatment; placebo rate 3.1% (monotherapy) |
| Injection site reactions | 7.4% (monotherapy); 11.1% (+TCS) | Pain, erythema, and swelling at injection site; placebo rate 4.1% (monotherapy), 0.8% (+TCS) |
| Eosinophilia | 1.4% (monotherapy); 1.2% (+TCS) | Transient rise peaking at week 4 (mean increase ~190 cells/mcL), returns to baseline with continued treatment; eosinophilia >5000 cells/mcL in 1.2% vs 0.3% placebo |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis / Angioedema | Rare | Any time after injection | Discontinue immediately; initiate emergency treatment; permanent discontinuation |
| Keratitis (including ulcerative keratitis) | 0.2% (0.9 events/100 subject-years) | Variable; during treatment period | Urgent ophthalmology referral; consider treatment interruption if severe or non-resolving |
| Keratoconjunctivitis (including atopic) | 0.3% (1.2 events/100 subject-years) | Variable | Ophthalmology evaluation; all events were non-serious and mild/moderate in trials |
| Severe hypersensitivity reactions | Very rare | Minutes to hours post-injection | Discontinue permanently; epinephrine and supportive care as indicated |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Injection site reaction | 0.3–0.4% | Across monotherapy and combination trials; pain and erythema most cited |
| Eosinophilia | 0.3% | Monotherapy trials only; transient elevations |
| Conjunctivitis | 0.4% | Combination TCS trial (ECZTRA 3); 2 subjects overall led to discontinuation |
Conjunctivitis is the most clinically significant ocular adverse effect with tralokinumab. Rates were approximately double those of placebo (7.5% vs 3.1%). However, most events were mild-to-moderate, non-serious, and resolved during the treatment period. In long-term extension data (ECZTEND), exposure-adjusted rates of conjunctivitis decreased over time. Patients should be counselled to report any new eye symptoms promptly. Preservative-free lubricating eye drops may be used for mild symptoms; persistent or worsening symptoms warrant ophthalmology referral.
Drug Interactions
Tralokinumab is a monoclonal antibody eliminated via proteolytic catabolism and does not interact with cytochrome P450 enzymes. A dedicated drug interaction study in atopic dermatitis patients confirmed no clinically significant effects on the pharmacokinetics of midazolam (CYP3A4), warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), or caffeine (CYP1A2) (FDA PI). Formal drug-drug interaction potential is therefore low. The main clinical considerations involve immunological interactions rather than metabolic ones.
Monitoring
-
Ocular Symptoms
Each visit
Routine Ask about new or worsening eye redness, itching, tearing, or visual changes at every clinic visit. Conjunctivitis occurs in ~7.5% and keratitis in ~0.2%. Ophthalmology referral warranted for persistent or vision-affecting symptoms. -
Disease Response (IGA, EASI)
Baseline, week 16, then Q12–16 weeks
Routine Assess IGA and EASI scores at week 16 to determine response. Consider discontinuation if no meaningful improvement by 16 weeks. For responders on Q4W dosing, monitor for loss of response. -
Eosinophil Count
Baseline, week 4
Trigger-based Transient eosinophilia peaks around week 4 and typically normalises with continued treatment. Check at baseline and consider repeating at week 4 if patient has pre-existing eosinophilic conditions or elevated baseline count. Clinical significance appears low per pooled safety data. -
Helminth Screening
Before initiation
Trigger-based Screen patients at risk for parasitic infections (endemic area residence, travel history) before starting treatment. Treat any existing helminth infection before initiating tralokinumab. -
Vaccination Status
Before initiation
Routine Complete all age-appropriate vaccinations, especially live vaccines, prior to treatment initiation. Avoid live vaccines during treatment. -
Injection Site
Each injection
Routine Inspect for pain, erythema, or swelling. Rotate injection sites between thigh, abdomen (avoiding 5 cm around navel), and upper arm (caregiver only).
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to tralokinumab-ldrm or any excipient (acetic acid, polysorbate 80, sodium acetate trihydrate, sodium chloride) (FDA PI)
Relative Contraindications (Specialist Input Recommended)
- Active helminth infection: IL-13 is involved in anti-parasitic immunity; treatment should be withheld until infection is treated and resolved
- Severe pre-existing ocular disease: Patients with active keratitis, severe conjunctivitis, or history of corneal complications may be at higher risk for ocular events; co-management with ophthalmology recommended
- Planned live vaccination: Live vaccines must be completed before starting tralokinumab or deferred until after treatment cessation
Use with Caution
- Pregnancy: Limited human data; IgG antibodies cross the placenta. Animal reproductive toxicity studies showed no adverse effects at doses up to 10× MRHD. A pregnancy exposure registry is available (1-877-311-8972 or mothertobaby.org)
- Lactation: Unknown whether tralokinumab is excreted in breast milk; maternal IgG is present in breast milk. Weigh developmental benefits of breastfeeding against clinical need
- Geriatric patients: Limited data in patients ≥65 years (77 subjects in pooled trials). No dedicated dose adjustment; use standard dosing with usual clinical vigilance
- Severe renal or hepatic impairment: Not studied; no dose adjustment expected for a monoclonal antibody but data are very limited
Tralokinumab does not carry an FDA Boxed Warning. However, the FDA label includes specific warnings regarding hypersensitivity reactions (including anaphylaxis and angioedema), conjunctivitis and keratitis, risk from helminth infections, and risk of infection from live vaccines. Prescribers should ensure patients are counselled on these risks and that live vaccinations are completed prior to initiation (FDA PI, Section 5).
Patient Counselling
Purpose of Therapy
Tralokinumab is a biologic medicine that targets a specific protein (IL-13) driving the inflammation behind eczema. It is used for moderate-to-severe atopic dermatitis when topical treatments alone are not enough. The goal is to reduce skin inflammation, itching, and flares so that patients experience better skin clearance and improved quality of life.
How to Take
Tralokinumab is given as an injection under the skin (subcutaneous). The first injection session uses a higher loading dose, followed by a regular maintenance dose every two weeks. Patients or caregivers should receive training from a healthcare provider on proper injection technique before self-administering. The medication should be allowed to reach room temperature for at least 30 minutes (prefilled syringe) or 45 minutes (autoinjector) before use. Injection sites should be rotated between the thigh, abdomen, or upper arm.
Sources
- ADBRY (tralokinumab-ldrm) injection, for subcutaneous use. Full Prescribing Information. LEO Pharma Inc. Revised 06/2024. FDA Label Primary source for dosing, adverse reactions, pharmacokinetics, contraindications, and all factual data in this monograph.
- Adtralza (tralokinumab) Summary of Product Characteristics. European Medicines Agency. EMA SmPC European labelling providing additional pharmacokinetic detail and weight-based dosing rationale.
- FDA Integrated Review: Application 761180Orig1s000 (Tralokinumab-ldrm). December 2021. FDA Review Comprehensive FDA clinical and pharmacology review supporting original approval decision.
- Wollenberg A, Blauvelt A, Guttman-Yassky E, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021;184(3):437–449. doi:10.1111/bjd.19574 Pivotal monotherapy trials establishing IGA 0/1 and EASI-75 efficacy at week 16 and maintenance through week 52.
- Silverberg JI, Toth D, Bieber T, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450–463. doi:10.1111/bjd.19573 Combination therapy trial demonstrating additive benefit of tralokinumab with TCS over TCS alone.
- Paller AS, Flohr C, Cork M, et al. Efficacy and safety of tralokinumab in adolescents with moderate to severe atopic dermatitis: the phase 3 ECZTRA 6 randomized clinical trial. JAMA Dermatol. 2023;159(6):596–605. doi:10.1001/jamadermatol.2023.0627 Phase 3 trial in adolescents (12–17 years) supporting the December 2023 paediatric label expansion.
- Merola JF, Bagel J, Almgren P, et al. Tralokinumab does not impact vaccine-induced immune responses: results from a 30-week, randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis. J Am Acad Dermatol. 2021;85(1):71–78. doi:10.1016/j.jaad.2021.03.032 ECZTRA 5 vaccine response study confirming non-live vaccine safety during tralokinumab treatment.
- Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43–e56. doi:10.1016/j.jaad.2023.08.102 Current AAD guidelines positioning biologics (including IL-13 inhibitors) in the AD treatment algorithm for adults.
- Popovic B, Breed J, Rees DG, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429(2):208–219. doi:10.1016/j.jmb.2016.12.005 Structural biology study elucidating how tralokinumab blocks IL-13 binding to both receptor subunits.
- Soehoel A, Nnane I, Guttman-Yassky E, et al. Population pharmacokinetics of tralokinumab in adult subjects with moderate to severe atopic dermatitis. Clin Pharmacol Drug Dev. 2022;11(8):997–1009. doi:10.1002/cpdd.1113 Population PK analysis characterising body-weight effects on exposure and supporting dose regimen selection.
- Oh CK, Faggioni R, Jin F, et al. An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males. Br J Clin Pharmacol. 2010;69(6):645–655. doi:10.1111/j.1365-2125.2010.03647.x Early PK study in healthy subjects establishing SC bioavailability estimates for tralokinumab.
- Simpson EL, Merola JF, Silverberg JI, et al. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022;187(6):888–899. doi:10.1111/bjd.21867 Pooled safety analysis across all completed trials providing the adverse event incidence rates cited in this monograph.