Ejulir (Dupilumab)
Biosimilar monoclonal antibody for type 2 inflammatory conditions
Quick Facts About Ejulir
Key Takeaways About Ejulir
- Biosimilar to Dupixent: Ejulir contains dupilumab and has been shown to be highly similar to the reference product in quality, safety, and efficacy
- Blocks type 2 inflammation: Works by inhibiting IL-4 and IL-13, the key drivers of Th2-mediated inflammatory conditions
- Multiple indications: Approved for atopic dermatitis, asthma, nasal polyps, prurigo nodularis, and eosinophilic esophagitis
- Self-administered injection: Given every 2 weeks (or weekly for some conditions) using a convenient pre-filled pen device
- Watch for eye symptoms: Conjunctivitis and eye-related side effects are more common in patients with atopic dermatitis
What Is Ejulir and What Is It Used For?
Ejulir is a biosimilar medicine containing dupilumab, a fully human monoclonal antibody that targets the interleukin-4 receptor alpha subunit (IL-4Rα). By blocking IL-4 and IL-13 signalling, it suppresses the type 2 (Th2) inflammatory cascade that drives conditions such as atopic dermatitis, asthma, and nasal polyps.
Ejulir belongs to a class of biologic medicines known as interleukin inhibitors. It was developed as a biosimilar to Dupixent (dupilumab), the first-in-class monoclonal antibody targeting the IL-4Rα pathway. Biosimilars undergo rigorous regulatory evaluation by agencies such as the European Medicines Agency (EMA) to demonstrate that they are highly similar to the reference product with no clinically meaningful differences in quality, safety, or efficacy.
The active substance, dupilumab, is a fully human immunoglobulin G subclass 4 (IgG4) monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. It specifically binds to the IL-4Rα subunit, which is the shared receptor component for both interleukin-4 (IL-4) and interleukin-13 (IL-13). These two cytokines are major drivers of type 2 inflammation, a pattern of immune activation that underlies several chronic inflammatory conditions.
By blocking IL-4Rα, Ejulir inhibits multiple downstream inflammatory processes simultaneously. IL-4 signalling via both type I and type II receptors is suppressed, along with IL-13 signalling through the type II receptor. This dual blockade results in reduced IgE antibody production, decreased eosinophil recruitment and activation, diminished mucus hypersecretion, and normalisation of the skin barrier in atopic dermatitis. Clinical trials with the reference product have demonstrated significant improvements in disease severity, itching, and quality of life across all approved indications.
Approved Indications
Ejulir is approved for several conditions driven by type 2 inflammation:
- Moderate-to-severe atopic dermatitis: In adults and adolescents aged 12 years and older who are candidates for systemic therapy. Atopic dermatitis (eczema) is a chronic inflammatory skin disease characterised by intense itching, redness, and skin barrier dysfunction.
- Severe asthma with type 2 inflammation: As add-on maintenance treatment in adults and adolescents aged 12 years and older whose asthma is inadequately controlled with high-dose inhaled corticosteroids plus another maintenance medication. Patients typically have elevated blood eosinophils and/or fractional exhaled nitric oxide (FeNO).
- Chronic rhinosinusitis with nasal polyps (CRSwNP): As add-on therapy with intranasal corticosteroids in adults with severe CRSwNP for whom systemic corticosteroids and/or surgery have not provided adequate disease control.
- Prurigo nodularis: Treatment of moderate-to-severe prurigo nodularis in adults who are candidates for systemic therapy. This is a chronic skin condition characterised by intensely itchy nodules.
- Eosinophilic esophagitis (EoE): Treatment in adults and adolescents aged 12 years and older (weighing at least 40 kg) who are inadequately controlled by, intolerant to, or not candidates for conventional therapy.
What Should You Know Before Taking Ejulir?
Before starting Ejulir, your doctor will assess your medical history, current medications, and any pre-existing conditions such as helminth (parasitic worm) infections or eye disorders. You should not use Ejulir if you are allergic to dupilumab or any of the other ingredients in the medicine.
Contraindications
The only absolute contraindication to Ejulir is known hypersensitivity to dupilumab or to any of the excipients listed in the formulation. Hypersensitivity reactions to monoclonal antibodies can range from mild injection site reactions to severe systemic reactions including anaphylaxis, although the latter is rare with dupilumab. If you have previously experienced a severe allergic reaction to dupilumab or any dupilumab-containing product, you must not use Ejulir.
Unlike many immunosuppressive therapies, dupilumab does not broadly suppress the immune system. It specifically targets the type 2 inflammatory pathway, which means it has a more favourable safety profile compared to traditional systemic immunosuppressants such as ciclosporin, methotrexate, or systemic corticosteroids. However, this targeted mechanism still requires careful medical supervision.
Warnings and Precautions
Several important warnings and precautions should be considered before and during treatment with Ejulir:
- Hypersensitivity reactions: Although rare, cases of anaphylaxis and angioedema have been reported with dupilumab. If a systemic hypersensitivity reaction occurs, treatment should be discontinued immediately and appropriate medical treatment initiated. Patients should be aware of the signs of allergic reactions and seek immediate medical attention if they experience difficulty breathing, swelling of the face or throat, or generalised hives.
- Eye disorders: Conjunctivitis, blepharitis, keratitis, dry eye, and eye pruritus occur more frequently in patients treated with dupilumab, particularly those with atopic dermatitis. Patients should be advised to report any new or worsening eye symptoms to their doctor. If conjunctivitis persists or keratitis develops, referral to an ophthalmologist should be considered.
- Helminth (parasitic) infections: Dupilumab may influence the immune response against helminth infections because IL-4 and IL-13 play roles in the host defence against parasites. Pre-existing helminth infections should be treated and resolved before initiating Ejulir therapy. If a patient becomes infected during treatment and does not respond to anti-helminth medication, dupilumab should be discontinued until the infection is cleared.
- Asthma management: Ejulir should not be used to treat acute asthma attacks or acute exacerbations. Patients should continue their existing asthma medications unless specifically instructed otherwise by their doctor. Systemic or inhaled corticosteroids should not be abruptly discontinued when starting Ejulir; any corticosteroid dose reductions should be gradual and carried out under medical supervision.
- Eosinophilic conditions: In rare cases, patients being treated for asthma may present with systemic eosinophilia, sometimes with features consistent with eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). This typically occurs when systemic corticosteroids are being tapered. Patients should be monitored for vasculitic rash, worsening pulmonary symptoms, cardiac complications, or neuropathy.
- Vaccinations: Live and live-attenuated vaccines should be avoided during treatment with Ejulir. Non-live (inactivated) vaccines may be administered, although the immune response to some vaccines may be slightly altered.
Pregnancy and Breastfeeding
There is limited clinical data on the use of dupilumab during pregnancy in humans. Animal reproductive toxicity studies have not revealed any harmful effects on fertility, embryo-foetal development, or postnatal development. However, as a precautionary measure, the use of Ejulir during pregnancy should be avoided unless the expected therapeutic benefit clearly outweighs any potential risk to the foetus.
As an IgG4 monoclonal antibody, dupilumab is expected to cross the placental barrier, particularly during the third trimester of pregnancy. The potential effects on the developing immune system of the unborn child are not fully characterised. Women of childbearing potential should discuss contraception and family planning with their healthcare provider before starting treatment.
It is unknown whether dupilumab is excreted in human breast milk. Human immunoglobulins (IgG) are known to be present in breast milk, especially in the first days after birth. A clinical decision must be made about whether to discontinue breastfeeding or to discontinue Ejulir therapy, taking into account the benefits of breastfeeding for the child and the benefits of continued treatment for the mother. Animal studies have not shown adverse effects on fertility.
How Does Ejulir Interact with Other Drugs?
Ejulir has a relatively low risk of drug-drug interactions compared to small-molecule immunosuppressants. However, live vaccines should be avoided during treatment, and caution is advised with drugs metabolised by certain CYP450 enzymes, as elevated IL-4 levels in inflammatory states may alter CYP enzyme activity.
As a monoclonal antibody, dupilumab is not metabolised by cytochrome P450 (CYP450) enzymes and does not directly inhibit or induce these enzymes. However, elevated levels of certain cytokines (including IL-4) during chronic inflammation can suppress the formation of CYP450 enzymes. When an inhibitor of these cytokines (such as dupilumab) is introduced or withdrawn, the CYP450 enzyme levels may return to normal or change, potentially affecting the metabolism of concomitant drugs that are CYP450 substrates.
This is particularly relevant for drugs with a narrow therapeutic index, where small changes in blood levels could have clinically significant effects. In practice, the clinical significance of this interaction appears to be limited for most patients, but monitoring may be warranted in certain situations.
| Drug / Drug Class | Interaction Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Live vaccines (e.g., MMR, varicella, yellow fever) | Immunological | Major | Avoid concurrent use. Complete vaccinations before starting Ejulir. |
| Warfarin | CYP450 (CYP2C9 substrate) | Moderate | Monitor INR closely when starting or stopping Ejulir. |
| Theophylline | CYP450 (CYP1A2 substrate) | Moderate | Monitor theophylline levels, especially narrow therapeutic index. |
| Ciclosporin | CYP450 (CYP3A4 substrate) | Moderate | Monitor drug levels. Consider dose adjustment if switching from ciclosporin to Ejulir. |
| Inactivated vaccines (e.g., influenza, COVID-19) | Immunological | Low | Can be administered. Response may be slightly reduced. |
| Topical corticosteroids | Complementary | Low | Can be used together. May allow dose reduction of topical steroids over time. |
Major Interactions
The most clinically important interaction is with live and live-attenuated vaccines. Because Ejulir modulates the immune system, the safety and efficacy of live vaccines during treatment have not been established. Patients should ideally complete all recommended vaccinations, including live vaccines, before initiating Ejulir therapy. If vaccination is required during treatment, only inactivated (non-live) vaccines should be used.
Minor Interactions
Interactions with CYP450 substrates are generally considered to be of minor clinical significance for most patients. The theoretical basis for these interactions relates to the normalisation of CYP450 enzyme activity as type 2 inflammation is controlled. Drugs with a narrow therapeutic index (such as warfarin and theophylline) warrant closer monitoring during the initial phase of treatment or when treatment is discontinued. No formal dose adjustments are routinely required, but therapeutic drug monitoring may be appropriate in individual cases.
Ejulir can be safely combined with topical therapies such as corticosteroids, calcineurin inhibitors, and emollients. In clinical trials, the combination of dupilumab with topical corticosteroids demonstrated superior efficacy compared to either treatment alone in atopic dermatitis. Similarly, in asthma, Ejulir is used as add-on therapy alongside existing inhaled corticosteroids and long-acting beta-agonists.
What Is the Correct Dosage of Ejulir?
The dosage of Ejulir depends on the condition being treated, the patient's age, and body weight. Most indications require an initial loading dose followed by maintenance injections every two weeks, while eosinophilic esophagitis requires weekly dosing. Treatment should be initiated by a healthcare professional experienced in the management of the relevant conditions.
Adults
| Indication | Loading Dose | Maintenance Dose | Frequency |
|---|---|---|---|
| Atopic Dermatitis | 600 mg (2 × 300 mg) | 300 mg | Every 2 weeks |
| Asthma | 400 mg (2 × 200 mg) or 600 mg (2 × 300 mg) | 200 mg or 300 mg | Every 2 weeks |
| CRSwNP | No loading dose | 300 mg | Every 2 weeks |
| Prurigo Nodularis | 600 mg (2 × 300 mg) | 300 mg | Every 2 weeks |
| Eosinophilic Esophagitis | No loading dose | 300 mg | Weekly |
For asthma, the choice between 200 mg and 300 mg maintenance dosing depends on the clinical profile. Patients with oral corticosteroid-dependent asthma or those with comorbid moderate-to-severe atopic dermatitis should receive 300 mg every two weeks. The 200 mg dose is suitable for patients with severe asthma who do not have these additional factors.
Children and Adolescents
The dosing in adolescents (12 years and older) depends on body weight:
Atopic Dermatitis – Adolescents (12–17 years)
- Body weight < 60 kg: Loading dose 400 mg (2 × 200 mg), then 200 mg every 2 weeks
- Body weight ≥ 60 kg: Loading dose 600 mg (2 × 300 mg), then 300 mg every 2 weeks
Asthma – Adolescents (12–17 years)
- Standard dose: Loading dose 400 mg, then 200 mg every 2 weeks
- With oral corticosteroid dependence or comorbid atopic dermatitis: Loading dose 600 mg, then 300 mg every 2 weeks
Ejulir is not currently approved for use in children under 12 years of age for the biosimilar product, although the reference product dupilumab has been studied and approved in younger age groups for certain indications. Always consult the most current prescribing information for age-specific guidance.
Elderly Patients
No dose adjustment is required for elderly patients. In clinical trials with dupilumab, there were no overall differences in safety or efficacy between patients aged 65 years and older and younger adults. However, as with any biologic therapy, the limited number of elderly patients enrolled in clinical trials means that greater sensitivity of some older individuals cannot be ruled out entirely. The pharmacokinetics of dupilumab are not significantly affected by age.
Missed Dose
If a dose of Ejulir is missed, the patient should inject the missed dose as soon as possible. Thereafter, dosing should resume at the regular scheduled time. If the missed dose is injected within 7 days of the scheduled date, the next dose should be given at the originally planned time. If more than 7 days have elapsed, the next dose should be administered at the time the missed dose is given, and a new schedule should be established from that date.
Overdose
There is no specific antidote for dupilumab overdose. In clinical trials, doses up to 600 mg every 2 weeks have been administered without dose-limiting toxicity. In the event of an overdose, the patient should be monitored for signs and symptoms of adverse reactions, and appropriate symptomatic and supportive treatment should be initiated as necessary. Dupilumab is not removed by haemodialysis.
What Are the Side Effects of Ejulir?
The most frequently reported side effects of Ejulir include injection site reactions, conjunctivitis (eye inflammation), and headache. Eye-related side effects are notably more common in patients with atopic dermatitis. Most side effects are mild to moderate in severity and tend to decrease in frequency with continued treatment.
The safety profile of dupilumab has been extensively characterised in large clinical trial programmes involving thousands of patients across multiple indications. As a biosimilar, Ejulir is expected to have a comparable safety profile to the reference product. The following side effects have been reported based on pooled data from clinical trials and post-marketing surveillance.
Very Common (affects more than 1 in 10 people)
- Injection site reactions (redness, swelling, pain, itching, bruising at injection site)
Common (affects 1 to 10 in 100 people)
- Conjunctivitis (eye inflammation, redness)
- Blepharitis (eyelid inflammation)
- Eye pruritus (itchy eyes)
- Dry eye
- Oral herpes (cold sores)
- Headache
- Eosinophilia (elevated eosinophil count)
Uncommon (affects 1 to 10 in 1,000 people)
- Allergic conjunctivitis
- Keratitis (corneal inflammation)
- Facial redness or flushing
- Arthralgia (joint pain)
Rare (affects fewer than 1 in 1,000 people)
- Serum sickness or serum sickness-like reactions
- Anaphylaxis
- Angioedema
Eye-related side effects deserve particular attention. In clinical trials for atopic dermatitis, conjunctivitis occurred in approximately 10–20% of dupilumab-treated patients compared to 2–5% of placebo-treated patients. The mechanism is not fully understood but may be related to the role of IL-13 in goblet cell function on the ocular surface. Most cases of conjunctivitis are mild to moderate and can be managed with lubricant eye drops, and most patients do not need to discontinue treatment.
Injection site reactions are the most common side effect overall, affecting approximately 15–20% of patients. These typically include redness, swelling, itching, or pain at the injection site. Reactions are generally mild, transient, and tend to decrease in frequency with continued treatment. Rotating injection sites and allowing the pre-filled pen to reach room temperature before injection can help minimise these reactions.
Transient eosinophilia (elevated blood eosinophil count) may occur during the initial weeks of treatment, particularly in patients with asthma. This is usually temporary and resolves within the first 12 weeks of therapy. In rare cases, marked and sustained eosinophilia may occur, which warrants clinical evaluation to exclude eosinophilic granulomatosis with polyangiitis (EGPA).
How Should You Store Ejulir?
Ejulir should be stored in a refrigerator at 2–8°C, protected from light, and must not be frozen. It may be kept at room temperature (up to 25°C) for a maximum of 14 days when needed for convenience.
Proper storage is essential to maintain the effectiveness and safety of biologic medicines like Ejulir. As a protein-based medicine, dupilumab can be degraded by extreme temperatures, freezing, vigorous shaking, or prolonged exposure to light.
- Refrigerator storage: Store at 2–8°C (36–46°F) in the original carton to protect from light. This is the preferred long-term storage method.
- Do not freeze: Freezing can damage the protein structure of the monoclonal antibody and render the medicine ineffective. If the pre-filled pen has been frozen, even accidentally, it should be discarded and not used.
- Room temperature storage: If refrigeration is not immediately available (e.g., during travel), Ejulir may be kept at room temperature up to 25°C (77°F) for a maximum of 14 days. Once removed from the refrigerator and stored at room temperature, the pen should be used within 14 days or discarded.
- Protect from light: Keep the pen in the original carton until ready to use. Do not expose to direct sunlight or intense artificial light.
- Do not shake: Vigorous shaking can cause protein aggregation and foam formation, which may affect the quality of the medicine.
- Keep out of reach of children: Store safely away from children, as the pre-filled pen contains a needle.
Before injection, remove the pre-filled pen from the refrigerator and allow it to reach room temperature for approximately 30–45 minutes. Do not use external heat sources (such as a microwave or warm water) to speed up the warming process. Inspect the solution through the viewing window before use. The solution should be clear to slightly opalescent and colourless to pale yellow. Do not use the medicine if it appears cloudy, discoloured, or contains visible particles.
After the expiry date printed on the label and carton, the medicine should not be used. Used pre-filled pens should be disposed of in a sharps disposal container in accordance with local regulations. Do not dispose of medicines in household waste or wastewater.
What Does Ejulir Contain?
Ejulir contains dupilumab as the active substance at a concentration of 6 mg/ml, along with pharmaceutical excipients that maintain the stability and pH of the solution.
Each pre-filled pen of Ejulir contains dupilumab as the active substance, formulated at a concentration of 6 mg/ml in a sterile, preservative-free solution. The excipients are carefully selected to maintain the protein stability, appropriate pH, and tonicity of the formulation throughout its shelf life.
Active Substance
- Dupilumab: A fully human IgG4 monoclonal antibody, concentration 6 mg/ml
Excipients (Inactive Ingredients)
The following excipients are typically present in dupilumab formulations (the exact excipient list for Ejulir may vary slightly; refer to the product packaging for the definitive list):
- L-arginine hydrochloride: Stabiliser that helps maintain protein stability
- L-histidine: Buffering agent to maintain optimal pH
- L-histidine hydrochloride monohydrate: Buffering agent
- Polysorbate 80: Surfactant that prevents protein aggregation
- Sodium acetate trihydrate: Buffering agent
- Acetic acid (glacial): pH adjustment agent
- Sucrose: Stabiliser and tonicity agent
- Water for injections: Solvent
The formulation does not contain preservatives. Each pre-filled pen is intended for single use only and should be discarded after the injection is administered. Patients with known allergies to any of the listed excipients should inform their healthcare provider before starting treatment.
Frequently Asked Questions About Ejulir
Ejulir is a biosimilar medicine containing dupilumab, a monoclonal antibody that blocks interleukin-4 (IL-4) and interleukin-13 (IL-13) signalling. By inhibiting these inflammatory proteins, Ejulir reduces type 2 (Th2) inflammation in conditions such as atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, prurigo nodularis, and eosinophilic esophagitis. It is administered as a subcutaneous injection using a pre-filled pen.
Ejulir is a biosimilar to Dupixent, meaning it contains the same active substance (dupilumab) and has been shown through rigorous regulatory evaluation to be highly similar in quality, safety, and efficacy. Biosimilars undergo comprehensive comparability studies reviewed by agencies such as the EMA. Ejulir may offer a more affordable alternative while providing the same therapeutic benefit.
The most common side effects include injection site reactions (redness, swelling, pain), conjunctivitis (eye inflammation), headache, oral herpes (cold sores), and eosinophilia. Eye-related side effects such as conjunctivitis, blepharitis, dry eye, and eye itching are notably more common in patients with atopic dermatitis. Most side effects are mild to moderate and tend to decrease with continued treatment.
For most indications (atopic dermatitis, asthma, nasal polyps, prurigo nodularis), Ejulir is given every two weeks after an initial loading dose. For eosinophilic esophagitis, it is administered weekly. Your doctor will determine the correct dose and schedule based on your condition, body weight, and response to treatment. The loading dose is typically given as two separate injections at different sites on the same day.
There is limited data on the use of dupilumab during pregnancy. Animal studies have not shown reproductive toxicity, but as a precaution, Ejulir should be avoided during pregnancy unless the potential benefit justifies the potential risk. It is unknown whether dupilumab passes into breast milk. Discuss the risks and benefits with your doctor to decide whether to continue breastfeeding or continue treatment.
Store Ejulir in a refrigerator at 2–8°C. Do not freeze. Keep the pen in its original carton to protect from light. If needed, it may be kept at room temperature (up to 25°C) for a maximum of 14 days. Once removed from the refrigerator, use within 14 days or discard. Do not expose to heat or direct sunlight. Allow the pen to reach room temperature for 30–45 minutes before injection.
References
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- Simpson EL, Bieber T, Guttman-Yassky E, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. New England Journal of Medicine. 2016;375(24):2335-2348. doi:10.1056/NEJMoa1610020.
- Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. New England Journal of Medicine. 2018;378(26):2486-2496. doi:10.1056/NEJMoa1804092.
- Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52). The Lancet. 2019;394(10209):1638-1650. doi:10.1016/S0140-6736(19)31881-1.
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd List, 2023. World Health Organization. Available at: www.who.int.
- British National Formulary (BNF). Dupilumab. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk.
- Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab clinical trials. British Journal of Dermatology. 2019;181(3):459-473. doi:10.1111/bjd.17869.
- European Medicines Agency (EMA). Guideline on similar biological medicinal products. CHMP/437/04 Rev 1. 2014. Available at: www.ema.europa.eu.
- Dellon ES, Rothenberg ME, Collins MH, et al. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. New England Journal of Medicine. 2022;387(25):2317-2330. doi:10.1056/NEJMoa2205982.
- Yosipovitch G, Mollanazar N, Stander S, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nature Medicine. 2023;29(5):1180-1190. doi:10.1038/s41591-023-02320-9.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in dermatology, immunology, and clinical pharmacology.
Evidence Framework: All medical claims follow the GRADE evidence framework. This article is based on Level 1A evidence from systematic reviews and randomised controlled trials published in peer-reviewed journals.
Conflict of Interest: No commercial funding. The iMedic editorial team has no financial relationships with pharmaceutical companies. All content is editorially independent.