Ilumya - Drug Monograph

Introduction

Ilumya (tildrakizumab-asmn) is a humanized IgG1/k monoclonal antibody biologic medication specifically designed to target interleukin-23 (IL-23). Developed by Sun Pharma, it received FDA approval in March 2018 for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Ilumya represents a targeted approach to psoriasis management by selectively inhibiting a key cytokine involved in the inflammatory pathway of psoriatic disease.

Mechanism of Action

Ilumya works through highly selective inhibition of interleukin-23 (IL-23). Specifically, it binds to the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor. IL-23 is a pro-inflammatory cytokine that plays a crucial role in the differentiation, proliferation, and survival of T-helper 17 (Th17) cells. These cells produce additional inflammatory cytokines, including IL-17, IL-22, and tumor necrosis factor-alpha (TNF-α), which drive the inflammation and abnormal keratinocyte proliferation characteristic of plaque psoriasis. By blocking IL-23 signaling, Ilumya interrupts this inflammatory cascade at a pivotal point, reducing the pathological processes that lead to psoriatic plaque formation.

Indications

Ilumya is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Dosage and Administration

• Recommended dosage: 100 mg administered by subcutaneous injection
• Initial dosing: Two 100 mg doses administered at weeks 0 and 4
• Maintenance dosing: 100 mg every 12 weeks thereafter
• Administration: Subcutaneous injection in the thigh, abdomen, or upper arm
• Special populations:

- No dosage adjustment required for elderly patients - Not recommended in patients with severe renal impairment or end-stage renal disease - Not recommended in patients with moderate or severe hepatic impairment - Safety and effectiveness in pediatric patients have not been established

Pharmacokinetics

• Absorption: Bioavailability approximately 73% following subcutaneous administration
• Distribution: Volume of distribution approximately 7.3 L, suggesting limited distribution beyond plasma and extracellular fluid
• Metabolism: Expected to be metabolized via proteolytic degradation into small peptides and amino acids, similar to other IgG antibodies
• Elimination: Clearance approximately 0.32 L/day with terminal half-life of approximately 23 days
• Time to steady state: Reached by week 16 with every-12-week dosing

Contraindications

Ilumya is contraindicated in patients with:

• History of serious hypersensitivity reaction to tildrakizumab or any of its excipients
• Active tuberculosis infection

Warnings and Precautions

• Infections: May increase risk of infections; caution in patients with chronic infection or history of recurrent infections
• Tuberculosis: Evaluate patients for tuberculosis infection prior to initiating treatment
• Hypersensitivity reactions: Angioedema and urticaria have been reported; discontinue if serious reaction occurs
• Hepatotoxicity: Liver enzyme elevations observed; monitor patients with pre-existing liver disease
• Immunizations: Avoid live vaccines during treatment; ensure patients are up-to-date with immunizations before initiation
• Theoretical malignancy risk: Due to immunosuppressive effects, theoretical risk of malignancy exists

Drug Interactions

• Live vaccines: Concurrent use not recommended due to potential for vaccine-related infections
• CYP450 substrates: May normalize levels of cytokines that regulate CYP450 enzymes; monitor drugs with narrow therapeutic indices
• Other biologics: Concurrent use with other immunosuppressive biologics may increase infection risk

Adverse Effects

• Upper respiratory infections (14%)
• Injection site reactions (7%)
• Diarrhea (3%)
• Headache (2%)
• Fatigue (1%)

• Serious infections (1.3%)
• Hypersensitivity reactions
• Hepatic enzyme elevations

Monitoring Parameters

• Baseline:

- Tuberculosis screening - Liver function tests - Complete blood count - Infection history assessment

• Ongoing:

- Signs and symptoms of infection - Liver function monitoring (if clinically indicated) - Psoriasis assessment (PASI scores) - Patient-reported outcomes - Hypersensitivity reactions

• Periodic:

- Tuberculosis screening (if risk factors present) - Skin cancer screening (theoretical risk)

Patient Education

• Administration: Proper injection technique and rotation of injection sites
• Infection recognition: Report signs of infection (fever, cough, flu-like symptoms)
• Allergic reactions: Seek immediate medical attention for swelling, difficulty breathing, or severe rash
• Storage: Refrigerate at 2°C to 8°C (36°F to 46°F); protect from light
• Missed dose: Administer as soon as possible, then resume regular schedule
• Pregnancy registry: Encourage participation if pregnancy occurs during treatment
• Concomitant medications: Inform healthcare providers of all medications being taken
• Vaccinations: Discuss vaccination status before starting treatment

References

1. FDA Prescribing Information: Ilumya (tildrakizumab-asmn). 2018. 2. Reich K, et al. Efficacy and safety of tildrakizumab versus placebo or etanercept for chronic plaque psoriasis: two phase 3 randomised controlled trials. Lancet. 2017;390(10091):276-286. 3. Papp KA, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis: 52-week results from two phase 3 randomized controlled trials. J Am Acad Dermatol. 2018;79(2):277-286. 4. Blauvelt A, et al. Tildrakizumab for moderate-to-severe plaque psoriasis: 5-year results from two phase 3 randomized controlled trials. Br J Dermatol. 2021;185(2):323-334. 5. Menter A, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072.