4.1. Therapeutic indications

Crohn's disease

Risankizumab is indicated for the treatment of patients 16 years and older with moderately to severely active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy, or if such therapies are not advisable.

Ulcerative colitis

Skyrizi is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy.

4.2. Posology and method of administration

Skyrizi is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which Skyrizi is indicated.

Posology

Crohn's disease

The recommended dose is 600 mg administered by intravenous infusion at Week 0, Week 4, and Week 8, followed by 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter. Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit by Week 24.

For the posology of the subcutaneous regimen, see section 4.2 of the Skyrizi 360 mg solution for injection in cartridge Summary of Product Characteristics.

Ulcerative colitis

The recommended induction dose is 1200 mg administered by intravenous (IV) infusion at Week 0, Week 4, and Week 8. Starting at Week 12 and every 8 weeks thereafter, the recommended maintenance dose is based on individual patient presentation:

• A dose of 180 mg administered by subcutaneous injection is recommended for patients with adequate improvement in disease activity after induction

• A dose of 360 mg administered by subcutaneous injection is recommended for patients with inadequate improvement in disease activity after induction

Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit by Week 24.

For the posology of the subsequent subcutaneous dosing regimen, see section 4.2 of the Skyrizi 180 mg and 360 mg solution for injection in cartridge Summary of Product Characteristics.

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.

Special populations

Elderly (aged 65 years and over)

No dose adjustment is required (see section 5.2).

There is limited information in subjects aged ≥65 years.

Renal or hepatic impairment

No specific studies were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of Skyrizi. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considered necessary (see section 5.2).

Paediatric population

The safety and efficacy of Skyrizi for the treatment of Crohn's disease in children and adolescents younger than 16 years of age have not yet been established. The safety and efficacy of Skyrizi in children aged 0-17 years for the treatment of ulcerative colitis have not yet been established. Currently available data are described in section 5.1 and 5.2 but no recommendation on posology can be made.

Overweight patients

No dose adjustment is required (see section 5.2).

Method of administration

Skyrizi is administered by intravenous infusion.

Skyrizi concentrate for solution for infusion is for intravenous use only. The 600 mg dose should be administered over at least one hour, and the 1 200 mg dose should be administered over at least two hours. For instructions on dilution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important active infections (e.g. active tuberculosis, see section 4.4).

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infections

Risankizumab may increase the risk of infection.

In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, risankizumab should be used with caution. Treatment with risankizumab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops such an infection or is not responding to standard therapy for the infection, the patient should be closely monitored and risankizumab should not be administered until the infection resolves.

Tuberculosis

Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB) infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Immunisations

Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should be considered according to current immunisation guidelines. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with risankizumab. Patients treated with risankizumab should not receive live vaccines during treatment and for at least 21 weeks after treatment (see section 5.2).

Hypersensitivity

Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of risankizumab (see section 4.8). If a serious hypersensitivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.

Excipients with known effect

Polysorbate

This medicinal product contains 2 mg of polysorbate 20 in each 600 mg dose and 4 mg of polysorbate 20 in each 1 200 mg dose. Polysorbates may cause allergic reactions.

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium‑free'.

4.5. Interaction with other medicinal products and other forms of interaction

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination. Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal product metabolising enzymes are not expected and no dose adjustment is needed (see section 5.2).

Concomitant immunosuppressive therapy

The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics, have not been evaluated.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential should use an effective method of contraception during treatment and for at least 21 weeks after treatment.

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of risankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of risankizumab during pregnancy.

Breast-feeding

It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from risankizumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to the woman.

Fertility

The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

4.7. Effects on ability to drive and use machines

Risankizumab has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn's disease and 26.2% in ulcerative colitis).

Tabulated list of adverse reactions

Adverse reactions for risankizumab from clinical studies (Table 1) are listed by MedDRA system organ class and are based on 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); and very rare (< 1/10 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: List of adverse reactions

System Organ Class

Frequency

Adverse reactions

Infections and infestations

Very common

Upper respiratory infectionsa

Common

Tinea infectionsb

Uncommon

Folliculitis

Nervous system disorders

Common

Headachec

Skin and subcutaneous tissue disorders

Common

Pruritus

Rash

Eczema

Uncommon

Urticaria

General disorders and administration site conditions

Common

Fatigued

Injection site reactionse

Immune system disorders

Rare

Anaphylactic reactions

a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis, laryngitis, peritonsillar abscess

b Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, onychomycosis, tinea infection

c Includes: headache, tension headache, sinus headache

d Includes: fatigue, asthenia malaise

e Includes: injection site bruising, erythema, haematoma, haemorrhage, irritation, pain, pruritus, reaction, swelling, induration, hypersensitivity, nodule, rash, urticaria, vesicles, warmth; infusion site erythema, extravasation, reaction, swelling

Description of selected adverse reactions

Psoriasis

Infections

Over the entire psoriasis programme including long-term exposure to risankizumab, the rate of infections was 75.5 events per 100 subject-years. The majority of cases were non-serious and mild to moderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infections was 1.7 events per 100 subject-years (see section 4.4).

Crohn's disease

The adverse drug reaction profile observed in patients with Crohn's disease treated with risankizumab was consistent with the adverse drug reaction profile observed in patients across indications. No new adverse reactions were identified in risankizumab Crohn's disease studies.

Infections

The majority of infections were non‑serious and mild to moderate in severity and did not lead to discontinuation of risankizumab.

The rate of infections in the pooled data from the 12-week induction studies was 83.3 events per 100 subject‑years in subjects treated with risankizumab 600 mg IV compared to 117.7 events per 100 subject‑years in placebo. The rate of serious infections was 3.4 events per 100 subject‑years in subjects treated with risankizumab 600 mg IV compared to 16.7 events per 100 subject‑years in placebo (see section 4.4).

The rate of infections in the 52-week maintenance study was 57.7 events per 100 subject‑years in subjects treated with risankizumab 360 mg SC after risankizumab induction compared to 76.0 events per 100 subject‑years in subjects who received placebo after risankizumab induction. The rate of serious infections was 6.0 events per 100 subject-years in subjects treated with risankizumab 360 mg SC after risankizumab induction compared to 5.0 events per 100 subject‑years in subjects who received placebo after risankizumab induction (see section 4.4).

Ulcerative colitis

Overall, the safety profile observed in patients with ulcerative colitis treated with risankizumab was consistent with the safety profile observed in patients across indications.

Infections

The rate of infections in the pooled data from the 12-week induction study was 78.3 events per 100 subject‑years in subjects treated with risankizumab 1 200 mg intravenously compared to 74.2 events per 100 subject‑years in placebo. The rate of serious infections was 3.0 events per 100 subject‑years in subjects treated with risankizumab 1 200 mg intravenously compared to 5.4 events per 100 subject‑years in placebo (see section 4.4).

The rate of infections in the 52-week maintenance study was 67.4 events per 100 subject‑years in subjects treated with risankizumab 180 mg subcutaneously and 56.5 events per 100 subject‑years in subjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to 64.6 events per 100 subject‑years in subjects who received placebo after risankizumab induction. The rate of serious infections was 1.1 events per 100 subject-years in subjects treated with risankizumab 180 mg subcutaneously and 0.6 events per 100 subject-years in subjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to 2.3 events per 100 subject‑years in subjects who received placebo after risankizumab induction (see section 4.4).

Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity with risankizumab. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

For subjects with Crohn's disease treated with risankizumab at the recommended IV induction and SC maintenance doses for up to 64 weeks in CD clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies were detected in 3.4% (2/58) and 0% (0/58) of evaluated subjects, respectively.

For subjects with ulcerative colitis treated with risankizumab at the recommended intravenous induction and subcutaneous maintenance doses (180 mg or 360 mg) for up to 64 weeks in ulcerative colitis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies were detected in 8.9% (8/90) and 6.7% (6/90) for the 180 mg SC dose, or 4.4% (4/91) and 2.2% (2/91) for the 360 mg SC dose, of evaluated subjects, respectively.

Antibodies to risankizumab including neutralizing antibodies were not associated with changes in clinical response or safety.

Elderly

There is limited safety information in subjects aged ≥65 years.

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 Yellow Card Scheme:

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9. Overdose

In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.