Risankizumab

Risankizumab is a humanized monoclonal IgG1/k antibody (produced in Chinese Hamster Ovarian cells, CHO cells) with anti-inflammatory and selective immunosuppressive activity. Risankizumab 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 response to risankizumab was significantly better compared to ustekinumab. The co-primary endpoint, appearance-free or almost appearance-free skin was achieved after 16 weeks of therapy in 84% and 88% of patients, respectively.

The expression of IL-23 mRNA is increased in psoriatic lesions compared to normal skin. Risankizumab as monoclonal IgG1 antibody binds specifically to interleukin 23A (IL-23A) and inhibits its interaction with the IL-23 receptor. As a result, Risankizumab inhibits the release of proinflammatory cytokines and chemokines. In exploratory studies in patients with psoriasis, inflammatory infiltrates in lesional tissue biopsies were reduced after administration of Risankizumab.

The efficacy and safety of Risankizumab was investigated in four multicenter, randomized, double-blind studies (UltIMMa-1, UltIMMa-2, IMMhance and IMMvent) in 2,109 study participants with moderate to severe plaque psoriasis. Risankizumab was tested in these studies against ustecizumab and adalimumab as well as placebo and showed better results in both the 16-week observation phase and the 52-week observation phase. 80% of the patients who achieved a clear skin appearance after 16 weeks remained free of symptoms for 1 year (Gordon KB et al. 2018).

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

Women of childbearing age must use a reliable method of contraception during 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 risankizumab in pregnant women. Animal studies have shown no evidence of direct or indirect adverse health effects in terms of reproductive toxicity. As a precaution, the use of risankizumab during pregnancy should be avoided.

Lactation: It is not known whether Risankizumab passes into breast milk. In humans, antibodies can be transferred to the newborn via milk in the first days after birth. For this short period, a risk to the newborn/infant cannot be excluded. A decision must be made whether breastfeeding should be interrupted or whether treatment with Risankizumab should be discontinued / treatment with Risankizumab should be interrupted. Both the benefit of breastfeeding for the child and the benefit of the therapy for the woman must be considered.

The drug is applied subcutaneously. The recommended dose is 150 mg (two 75 mg injections), administered as a subcutaneous injection in week 0, week 4 and then every 12 weeks. In patients who do not show a response after 16 weeks of treatment, discontinuation of treatment should be considered. Some patients with an initial partial response may improve over the course of treatment beyond 16 weeks.

If a patient shows no response after 16 weeks of treatment, discontinuation of treatment should be considered. Some patients with an initial partial response may improve over the course of treatment beyond 16 weeks.

Elderly patients (over 65 years of age): There are no dose adjustments, but there is limited experience.

The most common possible adverse effects include:

• upper respiratory tract infections (13%)
• other side effects may be:
• filamentous fungal diseases of the skin
• Folliculars
• Headache
• Pruritus
• Fatigue
• Reactions at the injection site

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

CYP450 enzymes: Companion drugs are not expected to affect the pharmacokinetics of risankizumab because risankizumab is eliminated from the body by general protein degradation processes without the involvement of cytochrome P450 enzymes (CYP450 enzymes) and is not eliminated by renal or hepatic routes. Furthermore, Risankizumab does not affect the pharmacokinetic properties of concomitant drugs that are either directly or indirectly metabolized by CYP450 enzymes

Risankizumab should not be combined with live vaccines.

Clinically relevant active infections, e.g. active tuberculosis. Risankizumab must not be used in patients with active tuberculosis. Before initiating treatment with Risankizumab, patients must be assessed for tuberculosis infection. Patients receiving risankizumab should be monitored during and after treatment for signs and symptoms of active tuberculosis. Anti-tuberculosis therapy should be carried out before initiating treatment with risankizumab in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.

Skyrizi® 75 mg solution for injection in a pre-filled syringe

1. Bilal J. et al (2018) A Systematic Review and Meta-Analysis of the Efficacy and Safety of the Interleukin (IL)-12/23 and IL-17 Inhibitors Ustekinumab, Secukinumab, Ixekizumab, Brodalumab, and Tildrakizumab for the treatment of moderate to severe plaque psoriasis. J Dermatologist Treat 29:569-578.
2. Banaszczyk K (2019). Risankizumab in the treatment of psoriasis - literature review. Reumatologia. 57:158-162.
3. Chen Z et al (2017) Novel Biologic Agents Targeting Interleukin-23 and Interleukin-17 for Moderate-to-Severe Psoriasis. Clin Drug Investig 37:891-899
4. Feagan BG et al (2018) Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. Lancet Gastroenterol Hepatol 3:671-680.
5. Gordon KB et al (2018) Efficacy and safety of risankizumab in patients with moderate to severe Crohn's disease: results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet 392:650-661.
6. Haugh IM et al (2018) Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis. Drug of Devel Ther 12:3879-3883.
7. McKeage K et al (2019) Risankizumab: First Global Approval. Drugs 79: 893-900.
8. Reich K et al (2019) Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet 394: 576-586.