The information below is based on the summary of product characteristics approved by regulatory authorities. For full details from the SmPC ,please click here: https://www.medicines.org.uk/emc/product/15012/smpc

Additional related ECCO e-Learning resources can be found under IBD Curriculum Topic 6.1-6.11

Introduction and Mechanism of Action

Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved in inflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.

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.

Dosing, administration

1) Crohn's disease

The recommended dose is 600 mg administered by intravenous infusion (over at least one hour) 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.

2) Ulcerative colitis

The recommended induction dose is 1200 mg administered by intravenous infusion (over at least two hours) 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.

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. 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 risankizumab. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considered necessary.

- Paediatric population: The safety and efficacy of risankizumab 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 risankizumab in children aged 0-17 years for the treatment of ulcerative colitis have not yet been established. Currently available data are described in the SmPC of the drug but no recommendation on posology can be made.

- Overweight patients: No dose adjustment is required.

Contraindications

- Hypersensitivity to the active substance or to any of the excipients.

- Clinically important active infections (e.g. active tuberculosis).

Adverse effects

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

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

Interactions with other Drugs

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.

Concomitant immunosuppressive therapy

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

Special warnings and precautions

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.
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.

Hypersensitivity

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

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.