Tildrakizumab

Ilumetri is indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of plaque psoriasis. Posology The recommended dose is 100 mg by subcutaneous injection at weeks 0, and 4 and every 12 weeks thereafter.

At the physician’s discretion, in patients with high disease burden or in patients above 90 kg of body weight a dose of 200 mg may provide greater efficacy. Consideration should be given to discontinuing treatment in patients who have shown no response after 28 weeks of treatment.

Some patients with initial partial response may subsequently improve with continued treatment beyond 28 weeks. Missed dose If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.

2). Renal or hepatic impairment Ilumetri has not been studied in these patient populations. No dose recommendations can be made. 2. Paediatric population The safety and efficacy of Ilumetri in children and adolescents below the age of 18 years have not yet been established.

No data are available. Method of administration This medicinal product is administered by subcutaneous injection. Injection sites should be alternated. Ilumetri should not be injected into areas where the skin is affected by plaque psoriasis or is tender, bruised, red, hard, thick, or scaly.

The pen must not be shaken. Each pen is for single use only. After proper training in subcutaneous injection technique, patients may self-inject Ilumetri if a physician determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients.

Patients should be instructed to inject the full amount of tildrakizumab according to the instructions provided in the package leaflet. Comprehensive instructions for administration are given in the package leaflet.

3%). Tabulated list of adverse reactions Adverse reactions from clinical studies (Table 1) are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); and not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 1. List of adverse reactions MedDRA System organ class Preferred term Frequency category Infections and infestations Upper respiratory tract infectionsa Very common Nervous system disorders Headache Common Gastroenteritis Common Diarrhoea Common Gastrointestinal disorders Nausea Common Back pain CommonGeneral disorders and administration site conditions Injection site pain Common aIncluding nasopharyngitis.

Long-term Safety The safety profile of tildrakizumab observed during the long-term extensions periods of reSURFACE 1 and reSURFACE 2 was consistent with that of the double-blind periods. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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Ilumya® (tildrakizumab injection) is indicated for the treatment of adult patients with moderate- to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 1 Pediatrics Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

4 Geriatrics).

1 Dosing Considerations • Ilumya (tildrakizumab injection) should be initiated and supervised by healthcare professionals experienced in the diagnosis and treatment of plaque psoriasis and familiar with the Ilumya efficacy and safety profile.

Patients may self-inject Ilumya if a healthcare professional determines that it is appropriate. 2 Recommended Dose and Dosage Adjustment The recommended dose of Ilumya is 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

Pediatrics (<18 years of age) Health Canada has not authorized an indication for pediatric use. Geriatrics (≥65 years of age) Safety and efficacy data in patients aged 65 years and older are limited. No dose adjustment is required. Duration of treatment Continuation of Ilumya should be reconsidered if a patient has not responded within 28 weeks of treatment onset.

4 Administration Ilumya is administered by subcutaneous injection. Ilumya can be injected by a healthcare professional or, after proper training in subcutaneous injection technique, patients may self- inject Ilumya if a healthcare professional determines that it is appropriate.

However, the physician should ensure appropriate follow-up of patients. Full instructions for use are provided in the package leaflet. Ilumya® (tildrakizumab injection) Product Monograph Page 5 of 36 Injections should not be administered into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis.

Ilumya does not contain any preservatives. Therefore, discard any unused product remaining in the pre-filled syringes or pre-filled pens (see 11 STORAGE, STABILITY AND DISPOSAL). The full amount of Ilumya 100 mg pre-filled syringe or pre-filled pen should be injected for each dose according to the directions provided in the respective “Instructions for Use” document.

5 Missed Dose Patients who miss a dose of Ilumya should be advised to inject this missed dose as soon as they become aware of it, and then follow with their next scheduled dose.

2%). 0%). 6%). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful for identifying and for approximating rates of adverse drug reactions in real-world use. The safety profile of Ilumya in patients with moderate to severe plaque psoriasis is based on pooled data from two phase 3 trials (reSURFACE 1 and reSURFACE 2).

A total of 1255 plaque psoriasis subjects were exposed to Ilumya 100 mg or 200 mg in these 2 trials (see 14 CLINICAL TRIALS). Of these, 642 subjects were exposed for at least 52 weeks, 587 for at least 78 weeks, 469 for at least 104 weeks, and 271 for at least 256 weeks to Ilumya 100 mg.

Table 2 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ilumya 100 mg group than the placebo group during the 12-week, placebo- controlled period of the pooled clinical trials, reSURFACE 1 and reSURFACE 2.

1. 9% in subjects Ilumya® (tildrakizumab injection) Product Monograph Page 9 of 36 treated with Ilumya 100 mg. 3% of subjects treated with placebo. 443 subjects per patient-year of exposure. 009 subjects treated with Ilumya 100 mg per patient-year of exposure.

7% of subjects treated with Ilumya 100 mg. 009 subjects treated with Ilumya 100 mg per patient-years of exposure) occurred in subjects treated in plaque psoriasis clinical trials with Ilumya 100 mg for up to 64 weeks (see 7 WARNINGS AND PRECAUTIONS, Immune, Hypersensitivity).

In the open-label, uncontrolled, extension period of the two Phase 3 clinical trials, no cases of drug-related anaphylaxis were reported. Two cases of drug-related hypersensitivity reactions (urticaria), were reported in subjects treated with 100 mg.

Immunogenicity As with all therapeutic proteins there is the potential for immunogenicity with Ilumya. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Comparison of incidence of antibodies between products by different tests may be misleading.

3% (51/615) of subjects developed antibodies to tildrakizumab. Of the subjects who developed anti-drug antibodies, 37% (19/51, or 3% of all subjects receiving Ilumya 100 mg) had neutralizing antibodies. Presence of neutralizing antibodies was associated with lower tildrakizumab concentrations and reduced efficacy.

Adverse Reactions through Weeks 52 and 64 and the extension period Through Week 52 (Phase 2b and reSURFACE 2) and Week 64 (reSURFACE 1), the types and the frequency of the adverse reactions in the Ilumya-treated patients were similar to that observed during the first 12 weeks of treatment.

6% […]

• Ilumya (tildrakizumab injection) is contraindicated in patients who are hypersensitive to tildrakizumab or to any ingredient in the formulation, including any non-medicinal ingredients, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

Ilumetri is indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. 3

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of plaque psoriasis. Posology The recommended dose is 100 mg by subcutaneous injection at weeks 0, and 4 and every 12 weeks thereafter.

At the physician’s discretion, in patients with high disease burden or in patients above 90 kg of body weight a dose of 200 mg may provide greater efficacy. Consideration should be given to discontinuing treatment in patients who have shown no response after 28 weeks of treatment.

Some patients with initial partial response may subsequently improve with continued treatment beyond 28 weeks. Missed dose If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.

2). Renal or hepatic impairment Ilumetri has not been studied in these patient populations. No dose recommendations can be made. 2. Paediatric population The safety and efficacy of Ilumetri in children and adolescents below the age of 18 years have not yet been established.

No data are available. Method of administration This medicinal product is administered by subcutaneous injection. Injection sites should be alternated. Ilumetri should not be injected into areas where the skin is affected by plaque psoriasis or is tender, bruised, red, hard, thick, or scaly.

The syringe or the pen must not be shaken. Each syringe or pen is for single use only. After proper training in subcutaneous injection technique, patients may self-inject Ilumetri if a physician determines that it is appropriate. However, the physician should ensure appropriate follow- up of patients.

Patients should be instructed to inject the full amount of tildrakizumab according to the instructions provided in the package leaflet. Comprehensive instructions for administration are given in the package leaflet.

3%). Tabulated list of adverse reactions Adverse reactions from clinical studies (Table 1) are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); and not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 6 Table 1. List of adverse reactions MedDRA System organ class Preferred term Frequency category Infections and infestations Upper respiratory tract infectionsa Very common Nervous system disorders Headache Common Gastrointestinal disorders Gastroenteritis Common Diarrhoea Common Nausea Common General disorders and administration site conditions Back pain Common Injection site pain Common aIncluding nasopharyngitis.

Long-term Safety The safety profile of tildrakizumab observed during the long-term extensions periods of reSURFACE 1 and reSURFACE 2 was consistent with that of the double-blind periods. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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