Mirikizumab

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 (7.9%, most frequently nasopharyngitis), headache (3.3%), rash (1.1%) and injection site reactions (8.7%, maintenance period).

Tabulated list of adverse reactions

Adverse reactions from clinical studies (table) 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, 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 in the mirikizumab maintenance study where mirikizumab treatment is administered as subcutaneous injection.
^d Reported in the mirikizumab induction study where mirikizumab treatment is administered as intravenous infusion.

Description of selected adverse reactions

Infusion-related hypersensitivity reactions (LUCENT-1, weeks 1-12)

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 (LUCENT-2, weeks 12-52)

Injection site reactions were reported in 8.7% 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.

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

In the first 12 weeks (LUCENT-1), ALT increased was reported in 0.4% mirikizumab-treated patients. AST increased was reported by 0.5% mirikizumab-treated patients. All adverse reactions were reported as mild to moderate in severity and non-serious.

Over all mirikizumab treatment periods in the ulcerative colitis 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) (2.0%), ≥ 5 x ULN (0.7%) and ≥ 10 x ULN (0.2%) and AST to ≥ 3 x ULN (2.1%), ≥ 5 x ULN (1.1%) and ≥ 10 x ULN (0.1%) in patients receiving mirikizumab. These elevations have been noted with and without concomitant elevations in total bilirubin.

Immunogenicity

With 12 months of treatment, up to 23% of mirikizumab-treated patients 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. No association was found between anti-mirikizumab antibodies and hypersensitivity or injection site reactions.