Adverse reactions : תופעות לוואי

4.8     Undesirable effects
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 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

MedDRA System organ class           Frequency              Adverse reaction Infections and infestations         Common                 Upper respiratory tract infectionsa Uncommon               Herpes zoster
Immune system disorders             Uncommon               Infusion-related hypersensitivity reactions Musculoskeletal and Connective      Common                 Arthralgia Tissue Disorders
Nervous system disorders            Common                 Headache
Skin and subcutaneous tissue        Common                 Rashb disorders
General disorders and                   Common                 Injection site reactionsc administration site conditions          Uncommon               Infusion site reactionsd Investigations                          Uncommon               Alanine aminotransferase increased Uncommon               Aspartate aminotransferase increased 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 (see section 4.4). 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.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il