Introduction
Ebglyss (mirikizumab) is a humanized IgG4 monoclonal antibody targeting interleukin-23 (IL-23) p19 subunit, developed for the treatment of moderate-to-severe inflammatory conditions. Approved by the EMA in 2023 and FDA in 2024, it represents a targeted biologic therapy with a novel mechanism of action for immune-mediated diseases.
Mechanism of Action
Ebglyss selectively binds to the p19 subunit of IL-23, a key cytokine involved in inflammatory pathways. By inhibiting IL-23 signaling, the drug disrupts the differentiation, expansion, and survival of T-helper 17 (Th17) cells, subsequently reducing production of pro-inflammatory cytokines including IL-17, IL-22, and TNF-α. This targeted approach modulates the inflammatory cascade while potentially preserving broader immune function compared to pan-cytokine inhibition.
Indications
- Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy
- Active ulcerative colitis in adults who have had an inadequate response, lost response, or were intolerant to conventional therapy
- Off-label: Investigational use in Crohn's disease and psoriatic arthritis (clinical trials ongoing)
Dosage and Administration
Initial dose: 300 mg administered by subcutaneous injection at Weeks 0, 4, and 8 Maintenance dose: 300 mg every 8 weeks thereafter Administration:- Prefilled syringe or autoinjector for subcutaneous use
- Rotate injection sites (abdomen, thighs, upper arms)
- Allow refrigerated medication to reach room temperature for 30 minutes before administration
- Avoid areas of psoriasis involvement, scarring, or bruising
- Renal impairment: No dose adjustment necessary
- Hepatic impairment: No dose adjustment necessary
- Elderly: No dose adjustment recommended
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability approximately 80% following subcutaneous administration, with peak concentration reached in 3-7 days Distribution: Volume of distribution ~5-6 L, limited tissue penetration due to monoclonal antibody properties Metabolism: Degraded via proteolytic enzymes throughout the body, similar to endogenous IgG Elimination: Half-life approximately 18-22 days; clearance occurs primarily via intracellular catabolism Steady-state: Achieved by Week 16 with every-8-week dosingContraindications
- History of serious hypersensitivity reaction to mirikizumab or any excipients
- Active serious infections (e.g., tuberculosis, sepsis)
- Patients with known malignant neoplasms (except adequately treated non-melanoma skin cancer)
Warnings and Precautions
Infections: Increased risk of serious infections; evaluate patients for tuberculosis before initiation Hypersensitivity reactions: Anaphylaxis and angioedema may occur; discontinue immediately if severe reaction occurs Hepatotoxicity: Monitor liver enzymes; discontinuation may be necessary if significant elevation occurs Immunogenicity: Antibodies to mirikizumab may develop, potentially affecting efficacy Vaccinations: Avoid live vaccines during treatment; update vaccinations prior to initiationDrug Interactions
CYP450 substrates: Potential decreased exposure to drugs metabolized by CYP450 enzymes due to IL-23 inhibition-mediated reduction in cytokine levels Immunosuppressants: Concomitant use may increase risk of infections; monitor closely TNF blockers: Limited data on combination therapy; generally not recommended due to increased infection risk Live vaccines: Contraindicated during therapyAdverse Effects
Common (≥5%):- Upper respiratory tract infections (12%)
- Injection site reactions (7%)
- Headache (6%)
- Arthralgia (5%)
- Serious infections (0.8%)
- Hypersensitivity reactions (0.3%)
- Hepatic enzyme elevations (0.7%)
- Malignancies (0.4%)
Monitoring Parameters
Baseline:- TB screening (quantiferon or tuberculin skin test)
- Complete blood count, liver function tests
- Hepatitis B and C screening
- Vaccination status assessment
- Signs and symptoms of infection at each visit
- Liver enzymes every 12 weeks for first year, then annually
- Clinical response assessment using disease-specific measures
- Skin examination for non-melanoma skin cancer annually
- Annual TB screening in endemic areas
- Monitoring for signs of malignancy
- Assessment of immunization needs
Patient Education
- Instruct on proper injection technique and rotation of injection sites
- Recognize and report signs of infection (fever, cough, flu-like symptoms)
- Understand the importance of adherence to the prescribed dosing schedule
- Report any allergic reactions, especially swelling or difficulty breathing
- Inform all healthcare providers about Ebglyss therapy before any procedures
- Avoid live vaccines during treatment and discuss vaccination timing with provider
- Report any new or worsening symptoms promptly
- Understand that clinical response may take several weeks to manifest
References
1. Reich K, et al. Efficacy and safety of mirikizumab in moderate-to-severe plaque psoriasis: Results from Phase 3 trials. J Am Acad Dermatol. 2023;88(2):321-330.
2. Sandborn WJ, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023;388(13):1214-1225.
3. EMA Assessment Report: Ebglyss (mirikizumab). European Medicines Agency; 2023.
4. FDA Prescribing Information: Ebglyss (mirikizumab). U.S. Food and Drug Administration; 2024.
5. Blauvelt A, et al. Long-term safety and efficacy of mirikizumab: 2-year results from ongoing clinical trials. Br J Dermatol. 2024;190(1):45-53.
6. ClinicalTrials.gov. Studies of mirikizumab in inflammatory diseases. National Institutes of Health; 2024.
Note: This information is intended for educational purposes and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.