Tildrakizumab

Tildrakizumab is a humanized IgG1/k monoclonal antibody (produced in Chinese Hamster Ovary cells, CHO cells) with anti-inflammatory and selective immunosuppressive effects. Tildrakizumab is used for the treatment of plaque psoriasis. The effects are based on the binding and inactivation of the cytokine interleukin-23 (IL-23).

The expression of IL-23p19 mRNA is increased in psoriatic lesions compared to normal skin. Tildrakizumab as a monoclonal IgG1/κ antibody specifically binds to the p19 protein subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. As a result, the release of proinflammatory cytokines and chemokines is inhibited. In exploratory studies in patients with psoriasis, inflammatory infiltrates in lesional tissue biopsies were reduced after administration of tildrakizumab. IL-23p19 expression in lesional skin biopsies decreased up to two weeks after therapy compared to baseline. Gene expression patterns indicate an attenuation of the local inflammatory response.

Adult patients with moderate to severe plaque psoriasis who have had an inadequate response to previous conventional systemic therapy and/or PUVA or who have a contraindication or intolerance to such therapies.

Women of childbearing potential must use a reliable method of contraception during therapy with tildrakizumab and for at least 17 weeks after the end of treatment.

Pregnancy: To date, there is no or very limited experience (less than 300 pregnancy outcomes) with the use of tildrakizumab in pregnant women. Animal studies have shown no evidence of direct or indirect adverse health effects related to reproductive toxicity. For precautionary reasons, use of tildrakizumab during pregnancy should be avoided.

Lactation: It is not known whether tildrakizumab passes into breast milk. Available toxicology data from Javanese monkeys at postnatal day 28 have shown negligible levels of tildrakizumab in milk. In humans, antibodies can be transferred to the newborn via milk in the first few days after birth. A risk for the child cannot be excluded for this short period.

The drug is injected subcutaneously and has a half-life of approximately 23 days. The recommended dose of tildrakizumab is 100 mg and is administered at weeks 0 and 4 and every 12 weeks thereafter. In patients with certain characteristics (e.g. high disease burden, body weight ≥ 90 kg), 200 mg may be more effective.

In patients who do not show a response after 28 weeks of treatment, discontinuation of treatment should be considered. Some patients with only a partial response at the start may improve over the course of treatment if treatment is continued beyond 28 weeks.

The most common possible adverse effects include:

• Upper respiratory tract infections
• headaches
• Gastroenteritis, nausea, diarrhea
• Pain at the injection site and back pain
• Tildrakizumab increases the risk of infectious diseases.

Risk of infection: Tildrakizumab has the potential to increase the risk of infection. Tildrakizumab should be used with caution in patients with a history of chronic infection, recurrent infection, or recent serious infection.

CYP450 enzymes: Concomitant medications are not expected to affect the pharmacokinetics of tildrakizumab because its elimination from the body occurs by general protein degradation processes without the involvement of cytochrome P450 enzymes (CYP450 enzymes) and it is not eliminated by renal or hepatic routes. Similarly, tildrakizumab does not affect the pharmacokinetic properties of concomitant drugs that are metabolized either directly or indirectly via CYP450 enzymes

Live vaccines: Tildrakizumab should not be combined with live vaccines.

Hypersensitivity to the active substance

clinically relevant active infections, e.g. active tuberculosis

Note: Tildrakizumab must not be used in patients with active tuberculosis. Before initiating treatment with tildrakizumab, patients should be assessed for tuberculosis infection. Patients receiving tildrakizumab should be monitored during and after treatment for possible signs of active tuberculosis. Antituberculous therapy should be administered prior to initiating treatment with tildrakizumab in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.

Tildrakizumab was approved as an injectable drug in the USA and EU in 2018 and in Switzerland in 2019 (Ilumetri®).

According to the pooled Phase IIb and Phase III analyses, 7.3% of patients treated with tildrakizumab produced antibodies against tildrakizumab. A discernible correlation between the formation of antibodies against tildrakizumab with regard to a reduction in efficacy and the occurrence of treatment-related adverse events could not be established.

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