Mirikizumab

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.

Mirikizumab may increase the risk of severe infection. 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.

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.

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.

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.

Fertility

The effect of mirikizumab on human fertility has not been evaluated.

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

Summary of the safety profile

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).

Tabulated list of adverse reactions

Adverse reactions from clinical studies 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).

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.

Description of selected adverse reactions

Infusion-related hypersensitivity reactions (induction therapy)

Infusion-related hypersensitivity reactions were reported in 0.4% of mirikizumab-treated patients. All infusion-related hypersensitivity reactions were reported as non-serious.

Injection site reactions (maintenance therapy)

Injection site reactions were reported in 10.8% of mirikizumab-treated patients. The most frequent reactions were injection site pain, injection site reaction and injection site erythema. These symptoms were reported as non-serious, mild and transient in nature.

The results described above were obtained with the original formulation of mirikizumab. In a double blind, 2-arm, randomised, single-dose, parallel design study in 60 healthy subjects comparing 200 mg mirikizumab (2 injections of 100 mg in a pre-filled syringe) of the original formulation with the revised formulation statistically significantly lower VAS pain scores were obtained with the revised (12.6) vs. the original formulation (26.1) 1 minute after injection.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased

In the first 12 weeks, ALT increased was reported in 0.6% mirikizumab-treated patients. AST increased was reported by 0.4% mirikizumab-treated patients. All adverse reactions were reported as mild to moderate in severity and non-serious.

Overall mirikizumab treatment periods in the ulcerative colitis and Crohn’s disease clinical development program (including the placebo-controlled and open label induction and maintenance periods), there have been elevations of ALT to ≥3 x upper limit of normal (ULN) (2.3%), ≥5 x ULN (0.7%) and ≥10 x ULN (0.2%) and AST to ≥3 x ULN (2.2 ), ≥5 x ULN (0.8) and ≥10 x ULN (0.1%) in patients receiving mirikizumab. These elevations have been noted with and without concomitant elevations in total bilirubin.

Immunogenicity

In the ulcerative colitis studies, up to 23% of mirikizumab-treated patients with 12 months of treatment developed anti-drug antibodies, most of which were of low titer and tested positive for neutralising activity. Higher antibody titers in approximately 2% of subjects treated with mirikizumab were associated with lower serum mirikizumab concentrations and reduced clinical response.

In the Crohn’s disease study, 12.7% of mirikizumab-treated patients with 12 months of treatment developed anti-drug antibodies, most of which were of low titer and tested positive for neutralising activity. There was no identified clinically significant effect of anti-drug antibodies on pharmacokinetics or effectiveness of mirikizumab.

No association was found between anti-mirikizumab antibodies and hypersensitivity or injection-related events in either the ulcerative colitis or the Crohn’s disease studies.