tildrakizumab

Action and Spectrum

Actions and Spectrum: 

• tildrakizumab is a monoclonal antibody used to treat moderate-to-severe plaque psoriasis in adults. Its mechanism of action involves binding to a protein called interleukin-23 (IL-23), which is involved in the inflammation and immune response pathways that contribute to psoriasis. 
• Specifically, tildrakizumab binds to the p19 subunit of IL-23, which prevents IL-23 from binding to its receptor on the surface of immune cells. This, in turn, reduces the production of inflammatory cytokines, including IL-17 and IL-22, responsible for the characteristic skin lesions in psoriasis. 
• tildrakizumab’s spectrum of activity is limited to psoriasis, as it specifically targets the IL-23 pathway that is involved in the pathogenesis of this condition. It does not have activity against other autoimmune or inflammatory conditions, as it does not affect other cytokine pathways involved in these conditions. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Upper respiratory tract infections 

1-10% 

Diarrhea 

Reaction at the injection site 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• tildrakizumab is contraindicated in patients with a known hypersensitivity to the medication or its components. Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving tildrakizumab. 

• tildrakizumab should also not be used in patients with active tuberculosis (TB) or a history of latent or active TB infection, as it may increase the risk of TB reactivation. Patients should be screened for TB before initiation of treatment with tildrakizumab. 

• Additionally, tildrakizumab should not be used in patients with active infections, including localized infections such as cellulitis or abscesses, until the infection has been adequately treated. tildrakizumab may increase the risk of infections, including severe or opportunistic infections, and patients should be monitored for signs and symptoms of infection during treatment. 

Caution: 

• tildrakizumab may increase the risk of infections, including severe or opportunistic infections, such as tuberculosis, herpes zoster, and bacterial, fungal, or viral infections. Patients should be monitored for signs and symptoms of infection during treatment and evaluated for latent tuberculosis infection before starting therapy with tildrakizumab. 
• tildrakizumab should be used cautiously in patients with a history of inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis, as exacerbations of these conditions have been reported in patients receiving tildrakizumab. 
• tildrakizumab should be used with caution in patients with a history of malignancy or who are at increased risk of malignancy, as the long-term effects of tildrakizumab on the risk of malignancy are unknown 
• tildrakizumab should be used with caution in patients with a history of immunosuppression or immunodeficiency, as the safety and efficacy of tildrakizumab in these patients have not been established. 
• tildrakizumab should be used with caution in pregnant or breastfeeding women, as the safety of this medication during pregnancy and lactation has not been established. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• tildrakizumab is a monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23). IL-23 is a cytokine that plays a critical role in the pathogenesis of psoriasis by promoting the differentiation and activation of T-helper 17 (Th17) cells, which produce inflammatory cytokines such as IL-17 and IL-22. 
• By binding to the p19 subunit of IL-23, tildrakizumab inhibits the binding of IL-23 to its receptor on the surface of immune cells. This, in turn, leads to a reduction in the activation of Th17 cells and a decrease in the production of inflammatory cytokines, ultimately reducing the severity of psoriasis symptoms. 

Pharmacodynamics: 

The pharmacodynamics of tildrakizumab is related to its mechanism of action, which involves selective binding to the p19 subunit of interleukin-23 (IL-23).  

IL-23 is a cytokine that plays a critical role in the pathogenesis of psoriasis by promoting the differentiation and activation of T-helper 17 (Th17) cells, which produce inflammatory cytokines such as IL-17 and IL-22. By binding to the p19 subunit of IL-23, tildrakizumab inhibits the binding of IL-23 to its receptor on the surface of immune cells.

This, in turn, leads to a reduction in the activation of Th17 cells and a decrease in the production of inflammatory cytokines, ultimately reducing the severity of psoriasis symptoms. 

Pharmacokinetics: 

Absorption 

tildrakizumab is administered via subcutaneous injection. It has a bioavailability of 73-80% and a peak plasma time of approximately six days.  

Distribution 

tildrakizumab has a volume of distribution of 10.8 L.  

Metabolism 

The metabolic pathway of tildrakizumab has not been fully characterized, but it is expected to degrade into small peptides and amino acids via catabolic pathways similar to endogenous IgG.  

Elimination and Excretion 

tildrakizumab has a long elimination half-life of approximately 23 days and a clearance of 0.32 L/day. It is primarily eliminated via catabolism and clearance by reticuloendothelial cells. 

Adminstartion

Administration: 

tildrakizumab is administered via subcutaneous injection. The recommended dose is 100 mg (1 mL) at weeks 0 and 4, followed by maintenance doses of 100 mg every 12 weeks. tildrakizumab can be self-administered by patients after proper training, or it can be administered by a healthcare professional.

The injection site should be rotated, and the solution should be inspected visually for particulate matter and discoloration before administration. tildrakizumab should not be administered intravenously or intramuscularly. Following the recommended dosing regimen is essential to achieve the best therapeutic outcomes and minimize the risk of adverse effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tildrakizumab 

Why do we use tildrakizumab? 

• tildrakizumab is a monoclonal antibody used to treat moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.  
• Plaque psoriasis is a chronic autoimmune skin disorder characterized by raised, scaly, red, and itchy patches on the skin. 
• tildrakizumab targets interleukin-23 (IL-23), a vital cytokine in developing and progressing psoriasis. By blocking the activity of IL-23, tildrakizumab can reduce inflammation and improve the symptoms of psoriasis.