Tildrakizumab

Introduction to Tildrakizumab

Tildrakizumab is a humanized IgG1/κ monoclonal antibody that specifically binds to the p19 subunit of interleukin-23 (IL-23). It was developed by Sun Pharma and approved by the FDA in 2018 for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Mechanism of Action

Tildrakizumab selectively inhibits the p19 subunit of IL-23, a key cytokine involved in the pathogenesis of psoriasis. By blocking IL-23, tildrakizumab disrupts the IL-23/Th17 axis, which plays a crucial role in the inflammatory cascade associated with psoriasis. This targeted approach helps reduce inflammation and the hyperproliferation of keratinocytes characteristic of psoriatic lesions.

Indications

Tildrakizumab is primarily indicated for:

  • Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

While its primary indication is for adult patients, research is ongoing to evaluate its potential use in pediatric populations with psoriasis.

Dosage and Administration

The recommended dosage for tildrakizumab in adults is:

  • 100 mg administered subcutaneously at Weeks 0 and 4, and every 12 weeks thereafter
  • For some patients with a high disease burden, 200 mg doses may be more effective

Tildrakizumab is administered via subcutaneous injection. It's important to rotate injection sites and avoid areas where the skin is tender, bruised, erythematous, or affected by psoriasis.

Efficacy

Clinical trials have demonstrated the efficacy of tildrakizumab in treating moderate-to-severe plaque psoriasis:

  • In Phase III trials (reSURFACE 1 and reSURFACE 2), a significant proportion of patients achieved PASI 75 (Psoriasis Area and Severity Index 75% improvement) by week 12
  • At week 12, 64% of patients receiving 100 mg and 61% receiving 200 mg achieved PASI 75, compared to 6% on placebo
  • Improvements in quality of life measures were also observed, with many patients reporting reduced impact of psoriasis on daily activities

Safety Profile

Tildrakizumab has demonstrated a favorable safety profile in clinical trials:

  • Most common adverse reactions (≥1%) include upper respiratory infections, injection site reactions, and diarrhea
  • Low rates of serious infections, malignancies, and major adverse cardiovascular events were reported
  • No dose-dependent increase in adverse events was observed between the 100 mg and 200 mg doses

As with other biologic agents, patients should be evaluated for tuberculosis before initiating treatment and monitored for signs of infection during therapy.

Pediatric Considerations

While tildrakizumab is not currently approved for use in pediatric patients, research is ongoing:

  • A Phase III trial (NCT03924427) is evaluating the safety and efficacy of tildrakizumab in pediatric patients aged 6-17 years with moderate-to-severe plaque psoriasis
  • Pediatricians should be aware of ongoing research and potential future applications in managing severe pediatric psoriasis cases
  • The long-term safety profile in pediatric populations is yet to be established

When considering biologic therapies for pediatric patients with psoriasis, it's crucial to weigh the potential benefits against the risks and lack of long-term safety data in this population.



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