mirikizumab (Rx)

>10%

Upper respiratory tract infections (8-14%)

1-10%

Injection site reactions (9%)

Arthralgia (2-7%)

Rash (4%)

Headache (4%)

Herpes viral infection (2%)

<1%

Hypersensitivity reactions (0.4%)

Frequency Not Defined

Hepatic enzyme elevations

Contraindications

History of serious hypersensitivity reaction to mirikizumab or any of its excipients

Cautions

Hypersensitivity reactions

• Serious hypersensitivity reactions, including anaphylaxis during IV infusion, reported
• Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction
• If severe hypersensitivity reaction occurs, discontinue immediately and initiate appropriate treatment

Infections

• May increase infection risk of infection
• Do not initiate in patients with a clinically important active infection until the infection resolves or is adequately treated
• In patients with chronic infection or a history of recurrent infection, consider risks and benefits before prescribing mirikizumab
• Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur
• If a serious infection develops or is nonresponsive to standard therapy, monitor closely and do not administer until infection resolves

Tuberculosis (TB) infection

• Evaluate for TB infection before initiating
• Do not administer to patients with active TB infection
• Initiate treatment of latent TB before administering
• Consider anti-TB therapy before initiation in patients with past history of latent or active TB in whom an adequate course of treatment cannot be confirmed
• Monitor for signs and symptoms of active TB during and after treatment

Hepatotoxicity

• A case of drug-induced liver injury (ALT 18x ULN; AST 10x ULN; total bilirubin 2.4x ULN) in conjunction with pruritus was reported in a clinical trial subject following a longer than recommended induction regimen
• In the trial, mirikizumab was discontinued and liver test abnormalities eventually returned to baseline
• Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment
• Monitor thereafter according to routine patient management
• Consider other treatment options in patients with evidence of liver cirrhosis
• Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury
• Interrupt treatment if drug-induced liver injury suspected, until this diagnosis is excluded
• Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction

Immunizations

• Avoid use of live vaccines in patients treated with mirikizumab
• Medications that interact with the immune system may increase risk of infection following administration of live vaccines
• Before initiating, complete all age-appropriate vaccinations according to current immunization guidelines
• No data are available on response to live or non-live vaccines in mirikizumab-treated patients

Pregnancy

Available data from case reports of mirikizumab use in pregnant females are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

However, monoclonal antibodies can be actively transported across the placenta, and mirikizumab may cause immunosuppression to the in utero-exposed infant

Pregnancy registry

• Monitor pregnancy outcomes in females exposed to mirikizumab during pregnancy
• Patients and healthcare providers are encouraged to call Eli Lilly and Company at 1-800-Lilly-Rx (1-800-545-5979)

Clinical considerations

• Disease-associated maternal and embryo/fetal risk

  • Risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity
  • Adverse pregnancy outcomes include preterm delivery (<37 weeks gestation), low birth weight (<2,500 g) infants, and small for gestational age at birth

• Fetal/neonatal adverse reactions

  • Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester
  • Because mirikizumab may interfere with immune response to infections, consider risks and benefits before administering live vaccines to infants exposed to mirikizumab in utero
  • There are no data regarding infant serum levels of mirikizumab at birth and the duration of persistence of mirikizumab in infant serum after birth
  • Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, consider a minimum of 2 months after birth because of the half-life of the product

Animal data

• An enhanced pre- and postnatal development study was conducted in cynomolgus monkeys administered mirikizumab IV during organogenesis to parturition at a dose of 300 mg/kg twice weekly (69 times the MRHD based on exposure comparisons)
• Mirikizumab crossed the placenta in monkeys
• No maternal toxicity was noted in this study
• No mirikizumab-related effects on morphological, functional or immunological development were observed in infant monkeys from birth through 6 months of age
• However, incidences of embryo/fetal loss were higher in the treated groups compared to control (6.7% [1 of 15] in controls vs 26.7% [4 of 15]), but were within the range of historical control data
• Following delivery, most adult female cynomolgus monkeys and all infants from the mirikizumab-treated group had measurable serum concentrations up to 28 days postpartum
• In infant monkeys, mean serum concentrations were ~4.8 times the respective mean maternal concentrations

Lactation

There are no data on presence of mirikizumab in human milk, effects on breastfed infants, or effects on milk production

Endogenous maternal IgG and monoclonal antibodies are transferred in human milk

Effects of local GI exposure and limited systemic exposure in breastfed infants to are unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Humanized IgG4 monoclonal antibody that binds to the p19 subunit of human interleukin 23 (anti-IL23p19), inhibiting interaction with IL-23 receptor

IL-23 is a naturally occurring cytokine that is involved in mucosal inflammation and affects the differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of pro-inflammatory cytokines

Mirikizumab inhibits release of pro-inflammatory cytokines and chemokines

Absorption

Bioavailability: 44% (SC)

Peak plasma time: 5 days (SC)

Peak plasma concentration: 99.7 mcg/mL (IV); 10.1 mcg/mL (SC)

Trough concentration: 2.75 mcg/mL (IV); 1.7 mcg/mL (SC)

AUC: 538 mcg⋅day/mL (IV); 160 mcg⋅day/mL (SC)

Distribution

Vd: 4.83 L

Metabolism

Expected to be degraded into small peptides and amino acids via catabolic pathways in same manner as endogenous IgG

Elimination

Half-life: 9.3 days

Clearance: 0.0229 L/hr

IV Incompatibilities

Do not mix with other drugs

IV Compatibilities

0.9% NaCl

D5W

IV Preparation

Visually inspect vial for particulate matter and discoloration; solution should appear clear to opalescent, colorless to slightly yellow to slightly brown, and free of visible particles; discard if it is cloudy or there are visible particles

Use an 18-21 gauge needle to withdraw 15 mL of solution from vial and transfer to a 50-250 mL infusion bag of 0.9% NaCl or D5W

Do not dilute or infuse through same IV line with solutions other than 0.9% NaCl or D5W

Do not shake; gently invert infusion bag to mix contents

Connect IV administration set (infusion line) to prepared infusion bag and prime IV line

Start infusion immediately after preparation, or store diluted solution as described below

SC Preparation

Full 200-mg maintenance dose requires 2 prefilled pens (ie, 100 mg/pen)

Intended for use under guidance and supervision of a healthcare professional; patients (or caregivers) may self-inject after training in SC injection technique

Before injection, remove prefilled pen from refrigerator and leave at room temperature for 30 minutes

Do not shake prefilled pens

Visually inspect for particulate matter and discoloration; solution should appear clear to opalescent, colorless to slightly yellow to slightly brown, and free of visible particles; discard if it is cloudy or there are visible particles

IV Administration

Administer IV infusion over at least 30 minutes

Flush IV line (at same rate as infusion) at the end of infusion with 0.9% NaCl or D5W

Time required to flush IV line is in addition to the minimum 30-minute infusion time

SC Administration

Sites for SC injection include abdomen, thigh, and back of upper arm

Inject in different location every time

Do not inject into areas where skin is tender, bruised, erythematous, or indurated

Does not contain preservatives; therefore, discard any unused product

Do not reuse

Missed dose

• Administer dose as soon as possible
• Thereafter, resume dosing every 4 weeks

Storage

Vial and prefilled pen are not made with dry natural rubber latex

Do not freeze; do not use if it has been frozen

Do not shake

Keep in original carton to protect from light until time of use

Product is sterile and preservative-free; discard any unused portion

Unopened vial

• Refrigerate at 2-8ºC (36-46ºF)

Diluted IV solution

• If not used immediately, refrigerate at 2-8ºC (36-46ºF)
• Use diluted infusion solution within 48 total hr, of which not more than 5 hr are permitted at nonrefrigerated temperatures not to exceed 25ºC (77ºF), starting from the time of vial puncture
• Keep away from direct heat or light
• Do not freeze diluted solution in prepared infusion bag

Prefilled pen

• Refrigerate at 2-8ºC (36-46ºF)
• If needed, may store at room temperature up to 30ºC (86ºF) for up to 2 weeks in original carton to protect from light
• Once stored at room temperature, do not return product to refrigerator
• Discard if these conditions are exceeded