SKYRIZI 75 mg / 150 mg Solution for injection Ref.[8750] Active ingredients: Risankizumab

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

If a serious hypersensitivity reaction, including anaphylaxis, occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.

Excipients with known effect

Skyrizi 150 mg solution for injection in pre-filled pen or pre-filled syringe:

This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled pen or pre-filled syringe, that is to say, essentially ‘sodium free’.

Skyrizi 75 mg solution for injection in pre-filled syringe:

This medicinal product contains 68.0 mg sorbitol per 150 mg dose.

The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say, essentially ‘sodium free’.

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 or phototherapy

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

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.

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

Summary of the safety profile

The most frequently reported adverse reactions were upper respiratory infections (13.0% in psoriasis).

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); very rare (<1/10 000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. List of adverse reaction:

^a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis, laryngitis, tracheitis
^b Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, onychomycosis, fungal skin infection
^c Includes: headache, tension headache, sinus headache
^d Includes: fatigue, asthenia
^e Includes: injection site bruising, erythema, haematoma, haemorrhage, irritation, pain, pruritus, reaction, swelling, induration, rash

Description of selected adverse reactions

Infections

The rate of infections was 75.5 events per 100 subject-years from the psoriasis clinical studies and 43.0 events per 100 subject-years from the psoriatic arthritis clinical studies, including long-term exposure to risankizumab. 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 from the psoriasis studies and 2.6 events per 100 subject-years from the psoriatic arthritis studies (see section 4.4).

Immunogenicity

For subjects treated with risankizumab at the recommended clinical dose for up to 52 weeks in psoriasis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies were detected in 24% (263/1 079) and 14% (150/1 079) of evaluated subjects, respectively. For subjects exposed to long term treatment of risankizumab (up to 204 weeks in the extension study), the immunogenicity profile observed was consistent compared to the first 52 weeks of treatment.

For most subjects with psoriasis, antibodies to risankizumab including neutralising antibodies were not associated with changes in clinical response or safety. Among the few subjects (approximately 1%; 7/1 000 at week 16 and 6/598 at week 52) with high antibody titres (>128), clinical response appeared to be reduced. The incidence of injection site reactions is numerically higher in the anti-drug antibody-positive groups compared with anti-drug antibody-negative groups over short-term (16 weeks: 2.7% vs 1.3%) and longer-term treatment (>52 weeks: 5.0% vs 3.3%). The injection site reactions were all mild to moderate in severity, none were serious, and none led to discontinuation of risankizumab.

For subjects treated with risankizumab at the recommended clinical dose for up to 28 weeks in psoriatic arthritis clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies were detected in 12.1% (79/652) and 0% (0/652) of evaluated subjects, respectively. Antibodies to risankizumab were not associated with changes in clinical response or safety for psoriatic arthritis.

Psoriatic arthritis

Overall, the safety profile observed in patients with psoriatic arthritis treated with risankizumab was consistent with the safety profile observed in patients with plaque psoriasis.

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 national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.