Tildrakizumab is a humanized monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders.
Trade name Ilumya
It is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis.
Targets IL23.
Pregnancy category AU: B1.
Routes of administration: Subcutaneous injection
It blocks interleukin-23 (IL-23), a cytokine that plays a key role in managing the immune system and autoimmune disease.
It is available as a single-dose prefilled syringe containing 100 mg of tildrakizumab in 1 ml of solution for subcutaneous administration.
It is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of the interleukin-23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor.
IL-23 plays a critical role in modulating inflammatory and immune responses.
The IL-23/Th17 pathway is crucial for the pathogenic mechanisms of psoriasis.
IL-23 acts at the top of the inflammatory pathway, activating the proliferation of pathogenic Th17 cells and subsequent production of proinflammatory cytokines, including IL-17.
IL-23 is a heterodimer with two subunits, p19 and p40.
The p40 subunit is also shared with IL-12, a cytokine that is involved in the immune response.
Treatments that targets the p40 subunit block both IL-23 and IL-12 and have been associated with an increased risk of infections.
Tildrakizumab binds only to the p19 subunit of IL-23, and this specific blockage, inhibits the release of proinflammatory cytokines and chemokines that mediate epidermal hyperplasia, keratinocyte immune activation, and tissue inflammation inherent in psoriasis.
It is available as a single-use, pre-filled syringe and is administered via subcutaneous injection.
The recommended dose is 100 mg at weeks 0, and 4 and every 12 weeks thereafter.
The drug has been studied in around 1,800 patients in two double-blind, randomized and controlled Phase-3 trials, titled reSURFACE 1 and reSURFACE 2,[13] followed by a 4-year extension period.
Tildrakizumab was proven to have superior efficacy to etanercept, an effective anti-TNFα treatment for psoriasis, with a significantly higher proportion of patients achieving responses at weeks 12 and 28.
After 3 years of continued treatment with tildrakizumab, response levels were well maintained in week 28 responders.
IL-23 targeting may only minimally impair the ability to generate a proper immune response.
Tildrakizumab most common (≥ 1%) side effects associated with treatment are upper respiratory infections, headache, gastroenteritis, nausea, diarrhea, injection site pain, and back pain.
In the reSURFACE 1 and 2 clinical trials, the overall incidence of side effects was low and comparable to placebo.