Overview
Lebrikizumab-lbkz is indicated for treating atopic dermatitis or eczema, a skin condition that causes itching, inflammation, dryness, and redness. The drug treats moderate to severe forms of eczema in cases where topical medications are ineffective in managing the condition. Lebrikizumab-lbkz is an IgG (Immunoglobulin G) monoclonal antibody that belongs to the interleukin-13 antagonist class of medication. It is mainly prescribed to treat atopic dermatitis in adult and pediatric patients of 12 years and above. The United States Food and Drug Administration (US FDA) approved the drug in September 2024 for treating this condition. Therefore, the article discusses Lebrikizumab-lbkz, its uses, side effects, contraindications, clinical pharmacology, and drug interactions.
Dose Form and Strength
The drug is available in injection form of strengths:
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Single-dose prefilled pen of 250 mg/2 mL (milligram per two milliliters).
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Single-dose prefilled syringe with needle shield of strength 250 mg/2 mL.
For Patients:
How Is Lebrikizumab-lbkz Used for Atopic Dermatitis?
Atopic dermatitis, also called eczema, is a chronic skin disease that causes redness, severe itching, inflammation, rashes, and skin discoloration. It is a long-lasting condition that usually appears in childhood and can continue until adulthood. This skin condition has no specific cause, and it can trigger various factors, such as environmental factors, allergens, or irritants.
Lebrikizumab-lbkz is a subcutaneous injection (a shot given under the skin) prescribed for treating atopic dermatitis in patients 12 years of age or older and weighing at least 88 pounds. It is mainly given to patients who do not respond well to other topical medications. The medication effectively relieves symptoms of atopic dermatitis, such as rashes, inflammation (swelling), redness, and itching.
How Should Lebrikizumab-lbkz Be Used?
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Lebrikizumab-lbkz is indicated for subcutaneous administration only.
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Lebrikizumab-lbkz should be used only under the guidance of your doctor. A person or caregiver should receive proper training in subcutaneous techniques for self-injecting the drug. Caregivers must learn the subcutaneous technique carefully for administering the drug to pediatric patients.
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The recommended site for injection is the thigh, abdomen, and upper arm (back side). Therefore, caregivers or doctors can inject the subcutaneous dosage of Lebrikizumab-lbkz at the back side of the upper arm.
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The injection site should be changed with every dosage, and one should avoid injection within five cm (centimeters) or two inches of the naval or anywhere in the skin that is bruised, tender, hard, and red.
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Also, one should keep the prefilled pen or injection syringe of Lebrikizumab-lbkz outside the refrigerator (at room temperature) for at least 45 minutes. The injection pen or syringe should not be introduced with any heating source to warm the injection.
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Before injecting, the injection solution must be checked for discoloration or particulate matter. In such cases, the injection should not be administered and discarded safely.
What Are the Side Effects of Lebrikizumab-lbkz?
Common Side Effects:
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Injection site reaction or pain.
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Herpes zoster or shingles (painful rash).
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Inflammation of the eye or eyelid, redness, itching, and swelling.
Serious Side Effects:
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Itching.
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Hives (swollen and itchy welts or bumps).
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Wheezing or breathing problems.
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Skin rash.
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Dizziness or fainting.
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Lightheadedness.
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Swelling of face, tongue, lips, mouth, and throat.
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Abdominal or stomach cramps.
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Worsening eye condition, such as blurred vision or change in vision.
Drug Dosage and Administration
Recommended Dose (Atopic Dermatitis):
The initial recommended dosage of Lebrikizumab-lbkz is 500 mg (milligram), two 250 mg injections at week 0 and week 2, followed by 250 mg every two weeks (or every 15 days) until week 16 or later until the desired clinical response is achieved.
Maintenance Dose:
The recommended maintenance dosage of Lebrikizumab-lbkz is 250 mg every four weeks.
Missed Dose
If a person misses the injection dose of Lebrikizumab-lbkz, they should administer it as soon as they remember. However, if it is already time for the next scheduled dose, the missed dose should be skipped, and the next one should be taken without fail. Do not take double drug dosage to compensate for the missed one. In case of confusion, one can reach out to their healthcare provider.
Overdose
In case of an overdose from Lebrikizumab-lbkz, contact the poison control department. In case a person faints, has seizures, and has trouble breathing, emergency medical help should be called immediately.
Drug Storage and Disposal
The drug should be refrigerated between two to eight degrees Celsius or 36 to 46 degrees Fahrenheit. The drug should not be stored at a temperature above 30 degrees Celsius or 86 degrees Fahrenheit. Also, Lebrikizumab-lbkz can be stored in its original carton at room temperature for up to seven days, and a syringe or pen can be stored for more than seven days. The drug should be protected from heat and light, not frozen or shaken.
Lebrikizumab-lbkz single-dose pen or syringe should be discarded safely after use, along with a needle, in a puncture-resistant container. Unneeded or expired medication should also be discarded safely through a take-back program by contacting the nearest pharmacist or local garbage or recycling authority. One can also dispose of the drug following FDA guidelines and protocols for safe disposal.
For Doctors:
Clinical Pharmacology
Mechanism of Action
An IgG4 monoclonal antibody, Lebrikizumab-lbkz, binds with slow off-rate and high to IL(interleukin)-13 and further binds to IL-13Rα1. The drug also inhibits the signaling of human IL-13 through a receptor complex IL-4Rα/IL-13Rα1. The drug also inhibits IL-13-induced responses, such as releasing proinflammatory chemokines, cytokines, and IgE. Additionally, Lebrikizumab-lbkz-bound IL-13 can bind IL-13Rα2, allowing IL-13 internalization and natural clearance.
Pharmacodynamics
Lebrikizumab-lbkz decreases the levels of serum periostin, CC chemokine, total immunoglobulin E (IgE), ligand (CCL)17 (a thymus and activation-regulated chemokine), CCL13 (a monocyte chemotactic protein-4), and CCL18 pulmonary and activation-regulated chemokine).
Pharmacokinetics
Absorption
After a subcutaneous dose of 250 mg of Lebrikizumab-lbkz, the drug reaches its peak plasma concentration in seven to eight hours. Its absolute bioavailability is 86 percent.
Distribution
Lebrikizumab-lbkz's distribution volume is 5.14 liters (174 ounces).
Metabolism
The drug is usually degraded into small amino acids and peptides through catabolic pathways, such as endogenous IgG (immunoglobulin G).
Elimination
The elimination half-life and the clearance rate of Lebrikizumab-lbkz are 24.5 days and 0.154 L/day (liters per day), respectively.
Ingredients
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Active Ingredient: Lebrikizumab-lbkz.
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Inactive Ingredients: Histidine, glacial acetic acid, sucrose, polysorbate 20, and water for injection.
Contraindications
Lebrikizumab-lbkz is contraindicated in patients with a known history of hypersensitivity reactions to the medication or any of its ingredients.
Drug Warnings and Precautions:
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Parasitic Infections (Helminth): Lebrikizumab-lbkz is known to increase the risk of parasitic (Helminth) infection due to its property of inhibiting IL-13 signaling. Therefore, doctors should treat a patient's pre-existing parasitic infection before prescribing the drug. Also, suppose a person gets an infection during treatment with the drug and does not respond to the treatment indicated for Helminth infection. In that case, Lebrikizumab-lbkz should be stopped until the patient recovers completely from the infection.
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Hypersensitivity: The drug is also known to cause hypersensitivity reactions, such as urticaria (or hives that cause rash, itching, and red bumps) and angioedema (skin and tissue swelling). Therefore, Lebrikizumab-lbkz should be discontinued if the patient experiences any such reaction.
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Keratitis and Conjunctivitis: Atopic dermatitis patients who received treatment with Lebrikizumab-lbkz are more prone to keratitis and conjunctivitis (eye disorders) than those receiving a placebo. However, most patients usually recover from these eye conditions during treatment. Therefore, the doctors should advise the patient to report any symptoms of eye condition they experience while taking the drug.
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Vaccinations: The drug can also alter one’s immunity and make them more prone to infections, especially after receiving live vaccines. Therefore, all vaccinations (age-appropriate) should be completed before receiving the drug as per the immunization protocols and guidelines. Also, live vaccines should be restricted before or during treatment with Lebrikizumab-lbkz.
Clinical Studies
Atopic Dermatitis:
Three multicenter, double-blind, randomized, placebo-controlled trials enrolled 1062 subjects of 12 years and older having moderate-to-severe atopic dermatitis, which was not effectively controlled by topical medications, and those who needed systemic therapy. 148 subjects (14 %) were 12 to more than 18 years old and weighed at least 2.20 pounds, and 914 (86 %) were adult subjects. Also, disease severity was defined by an Investigator’s Global Assessment or IGA score greater than or equal to three in the overall assessment of atopic dermatitis lesions on a severity scale of zero to four, an eczema area and severity index or EASI score greater than or equal to 16 on a scale of zero to 72, and a minimum body surface area involvement of greater than or equal to 10 percent.
At baseline, 50 percent of subjects were male, 63 percent were White, 11 percent were African American or Black, 21 percent were Asian, 12.8 percent identified as Latino or Hispanic, 63 percent of subjects had a baseline IGA score of three or moderate atopic dermatitis, and 37 percent of subjects had a baseline IGA of four that is severe atopic dermatitis. The baseline mean EASI was 29, and the baseline Pruritus NRS (Numeric Rating Scale) was seven on a scale of zero to ten. Of all subjects, 99 percent had received prior treatment for atopic dermatitis.
In all three trials, subjects in the Lebrikizumab-lbkz group received subcutaneous injections of Lebrikizumab-lbx 500 mg (milligram) at week 0 and week 2, followed by 250 mg every other week up to week 16.
To evaluate the maintenance and durability of response in the monotherapy trials, that is ADvocate 1 and ADvocate 2, subjects originally randomized to Lebrikizumab-lbkz who achieved an IGA score of zero or one, or at least a 75 percent reduction in EASI from baseline [EASI-75] at Week 16 and did not require rescue therapy were re-randomized to an additional 36 weeks of either a maintenance dose of Lebrikizumab-lbkz 250 mg (every two weeks), Lebrikizumab-lbkz 250 mg Q4W (every four weeks), or placebo.
In the concomitant therapy trial, subjects received Lebrikizumab-lbkz + TCS or placebo + TCS. Topical calcineurin inhibitors (TCI) were permitted for sensitive areas, such as the neck, face, intertriginous, and genital areas.
All three trials assessed the primary endpoint, the proportion of subjects who achieved an IGA score of zero (clear) or one (almost clear) and at least a 2-point improvement from baseline at Week 16. Other evaluated outcomes at week 16 included the proportion of subjects with EASI-75 and EASI-90 and improvement in itching severity as defined by a reduction of at least four points on an 11-point Pruritus NRS. ADvocate 1 and ADvocate 2 also evaluated the maintenance and durability of response through Week 52
Drug Interactions
Lebrikizumab-lbkz’s interactions with other medications have not been studied.
Use in Specific Populations:
Pregnancy
There is no sufficient data to evaluate the drug (Lebrikizumab-lbkz)-)-associated risks in pregnancy, such as birth defects, miscarriages, and other fetal and maternal health outcomes. However, the drug can get transmitted to the fetus through the mother via the placenta. This is because as the pregnancy progresses with time and reaches a peak, IgG antibody transportation also increases across the placenta, especially during the third trimester.
Breastfeeding
No specific data shows Lebrikizumab-lbkz in human milk or its effects on milk production or breastfed infants. However, human IgG antibodies get transferred to human milk. Therefore, the potential benefits of the drug, the clinical needs of the mother, and harmful effects on the fetus should be evaluated carefully before prescribing the drug to this population group.
Geriatric Use
Lebrikizumab-lbkz's safety and effectiveness in this population group have yet to be established as the clinical studies did not include sufficient subjects. Therefore, the drug should be carefully prescribed to this population group after evaluating the patient's clinical needs and the potential benefits of Lebrikizumab-lbkz.
Pediatric Use
The safety and effectiveness of Lebrikizumab-lbkz have been established in this population of 12 years and above (and of 2.2 pounds) for treating atopic dermatitis. However, the drug is not indicated for treating patients younger than 12 years and less than 40 kilograms (kg).
