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/14881/smpc

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

Introduction and Mechanism of Action

Mirikizumab is a humanised IgG4 monoclonal, anti-interleukin-23 (anti-IL-23) antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor.

IL-23, a regulatory cytokine, affects the differentiation, expansion, and survival of T cell subsets, (e.g., Th17 cells and Tc17 cells) and innate immune cell subsets, which represent sources of effector cytokines, including IL-17A, IL-17F and IL-22 that drive inflammatory disease. In humans, selective blockade of IL-23 was shown to normalise production of these cytokines.

Therapeutic indications

Ulcerative colitis

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

Crohn's disease

Mirikizumab is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment.

Dosing, administration

1) Ulcerative colitis

- Induction dose: The induction dose is 300 mg by intravenous infusion for at least 30 minutes at weeks 0, 4 and 8.

- Maintenance dose: The maintenance dose is 200 mg (i.e. two 100 mg pre-filled syringes or pens) by subcutaneous injection every 4 weeks after completion of induction dosing.

Patients should be evaluated after the 12-week induction dosing and if there is adequate therapeutic response, transition to maintenance dosing. For patients who do not achieve adequate therapeutic benefit at week 12 of induction dosing, mirikizumab 300 mg by intravenous infusion may be continued at weeks 12, 16 and 20 (extended induction therapy). If therapeutic benefit is achieved with the additional intravenous therapy, patients may initiate mirikizumab subcutaneous maintenance dosing (200 mg) every 4 weeks, starting at week 24. Mirikizumab should be discontinued in patients who do not show evidence of therapeutic benefit to extended induction therapy by week 24.

Patients with loss of therapeutic response during maintenance treatment may receive 300 mg mirikizumab by intravenous infusion every 4 weeks, for a total of 3 doses (re-induction). If clinical benefit is achieved from this additional intravenous therapy, patients may resume mirikizumab subcutaneous dosing every 4 weeks. The efficacy and safety of repeated re-induction therapy have not been evaluated.

2) Crohn's disease

- Induction dose: The induction dose is 900 mg (3 vials of 300 mg each) by intravenous infusion for at least 90 minutes at weeks 0, 4 and 8.

- Maintenance dose: The maintenance dose is 300 mg (i.e. one pre-filled syringe or pen of 100 mg and one pre-filled syringe or pen of 200 mg) by subcutaneous injection every 4 weeks after completion of induction dosing. The injections may be administered in any order.

The 200 mg pre-filled syringe and 200 mg pre-filled pen are only for the treatment of Crohn's disease.

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

Special populations

- Elderly: No dose adjustment is required. There is limited information in subjects aged ≥ 75 years.

- Renal or hepatic impairment: Mirikizumab has not been studied in these patient populations. 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 mirikizumab in children and adolescents aged 2 to less than 18 years have not yet been established. No data are available.

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 are upper respiratory tract infections (9.8 %, most frequently nasopharyngitis), headache (3.2 %), rash (1.3 %) and injection site reactions (10.8 %, maintenance period).

Adverse reactions from clinical studies (Table 1) are listed by MedDRA system organ class. The frequency category for each reaction is 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).

Table 1: Adverse reactions

^a Includes: acute sinusitis, COVID-19, nasopharyngitis, oropharyngeal discomfort, oropharyngeal pain, pharyngitis, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, and viral upper respiratory tract infection.

^b Includes: rash, rash macular, rash maculo-papular, and rash papular and rash pruritic.

^c Reported during mirikizumab maintenance therapy where mirikizumab treatment is administered as subcutaneous injection.

^d Reported during mirikizumab induction therapy where mirikizumab treatment is administered as intravenous infusion.

Interactions with other Drugs

No interaction studies have been performed. In clinical studies, concomitant use of corticosteroids or oral immunomodulators did not influence the safety of mirikizumab.

Population pharmacokinetic data analyses indicated that the clearance of mirikizumab was not impacted by concomitant administration of 5-ASAs (5-aminosalicylic acid), corticosteroids or oral immunomodulators (azathioprine, 6-mercaptopurine, thioguanine, and methotrexate).

Special warnings and precautions

Hypersensitivity reactions

In clinical studies, hypersensitivity reactions have been reported. Most were mild or moderate, severe reactions were uncommon. If a serious hypersensitivity reaction, including anaphylaxis, occurs, mirikizumab must be discontinued immediately and appropriate therapy must be initiated.

Infections

Mirikizumab may increase the risk of severe infection. Treatment with mirikizumab should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. The risks and benefits of treatment should be considered prior to initiating use of mirikizumab in patients with a chronic infection or a history of recurrent infection.
If a serious infection develops, discontinuation of mirikizumab should be considered until the infection resolves.

Pre-treatment evaluation for tuberculosis

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

Hepatic enzyme elevations

Cases of drug-induced liver injury (including one case meeting Hy's Law criteria) occurred in patients receiving mirikizumab in clinical trials. Liver enzymes and bilirubin should be evaluated at baseline and monthly during induction (including extended induction period, if applicable). Thereafter, liver enzymes and bilirubin should be monitored (every 1 - 4 months) according to standard practice for patient management and as clinically indicated. If increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are observed and drug-induced liver injury is suspected, mirikizumab must be discontinued until this diagnosis is excluded.

Immunisations

Prior to initiating therapy with mirikizumab, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Avoid use of live vaccines in patients treated with mirikizumab. No data are available on the response to live or non-live vaccines.

Women of childbearing potential

Women of childbearing potential should use an effective method of contraception during treatment and for at least 10 weeks after treatment.

Pregnancy

There is a limited amount of data from the use of mirikizumab 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 mirikizumab during pregnancy.

Breast-feeding

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