Mirikizumab-mrkz (Monograph)

Brand name: Omvoh
Drug class: Immunomodulatory Agents

Introduction

Mirikizumab-mrkz, a humanized immunoglobulin G4 (IgG4) monoclonal antibody, is an interleukin-23 antagonist.

Uses for Mirikizumab-mrkz

Mirikizumab has the following uses:

Mirikizumab-mrkz is indicated for the treatment of moderately to severely active ulcerative colitis in adults.

Mirikizumab-mrkz Dosage and Administration

General

Mirikizumab-mrkz is available in the following dosage form(s) and strength(s):

• Injection, for IV infusion after dilution: 300 mg/15 mL (20 mg/mL) solution in a single-dose vial

• Injection, for subcutaneous administration: 100 mg/mL solution in a single-dose prefilled pen

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Prior to treatment initiation, evaluate patients for tuberculosis (TB) infection, obtain appropriate tests (i.e., liver enzymes, bilirubin levels), and complete all age-appropriate vaccinations according to current immunization guidelines.

• The recommended induction dosage is 300 mg administered by IV infusion over at least 30 minutes at Weeks 0, 4, and 8.

• The recommended maintenance dosage is 200 mg administered by subcutaneous injection (given as two consecutive injections of 100 mg each) at Week 12, and every 4 weeks thereafter.

• See the full prescribing information for preparation, administration, and storage information for IV infusion and subcutaneous injection.

Related/similar drugs

Entyvio, Zeposia, dexamethasone, hydrocortisone, Humira, Stelara, Remicade

Cautions for Mirikizumab-mrkz

Contraindications

History of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients.

Warnings/Precautions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis during IV infusion, have been reported with mirikizumab administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction. If a severe hypersensitivity reaction occurs, discontinue mirikizumab immediately and initiate appropriate treatment.

Infections

Mirikizumab may increase the risk of infection.

Do not initiate treatment with mirikizumab in patients with a clinically important active infection until the infection resolves or is adequately treated.

In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to 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 an infection is not responding to standard therapy, monitor the patient closely and do not administer mirikizumab until the infection resolves.

Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with mirikizumab.

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

In clinical trials, subjects were excluded if they had evidence of active TB, a past history of active TB, or were diagnosed with latent TB at screening.

Hepatotoxicity

A case of drug-induced liver injury (alanine aminotransferase [ALT] 18 times the upper limit of normal (ULN), aspartate aminotransferase [AST] 10 times the ULN, and total bilirubin 2.4 times the ULN) in conjunction with pruritus was reported in a clinical trial subject following a longer than recommended induction regimen. Mirikizumab was discontinued. 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 is 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 the risk of infection following administration of live vaccines. Prior to initiating therapy with mirikizumab, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or non-live vaccines in patients treated with mirikizumab.

Specific Populations

Pregnancy

There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mirikizumab during pregnancy. Pregnant women exposed to mirikizumab and healthcare providers are encouraged to call Eli Lilly and Company at 1-800-Lilly-Rx (1-800-545-5979).

Available data from case reports of mirikizumab-mrkz use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Although there are no data on mirikizumab-mrkz, monoclonal antibodies can be actively transported across the placenta, and mirikizumab-mrkz may cause immunosuppression in the in utero-exposed infant. An enhanced pre- and post-natal development study conducted in pregnant monkeys at a dose 69 times the maximum recommended human dose (MRHD) revealed no adverse developmental effects to the developing fetus, or harm to infant monkeys from birth through 6 months of age. There are risks of adverse pregnancy outcomes associated with increased disease activity in women with inflammatory bowel disease.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

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

Lactation

There are no data on the presence of mirikizumab-mrkz in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred in human milk. The effects of local GI exposure and limited systemic exposure in the breastfed infant to mirikizumab-mrkz are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mirikizumab and any potential adverse effects on the breastfed infant from mirikizumab or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of mirikizumab have not been established in pediatric patients.

Geriatric Use

Of the 795 mirikizumab-treated subjects in the two clinical trials, 64 subjects (8%) were 65 years of age and older, while 10 subjects (1%) were 75 years of age and older. These clinical studies did not include sufficient numbers of subjects 65 years of age and over to determine whether they respond differently from younger adult subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. No clinically meaningful differences in the pharmacokinetics of mirikizumab-mrkz were observed in subjects 65 years of age and older compared to younger adult subjects.

Common Adverse Effects

• Most common adverse reactions (≥2%) in the induction study: upper respiratory tract infections and arthralgia.

• Most common adverse reactions (≥2%) in the maintenance study: upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor.

IL-23 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. Research in animal models has shown that pharmacologic inhibition of IL-23p19 can ameliorate intestinal inflammation.

Mirikizumab-mrkz inhibits the release of pro-inflammatory cytokines and chemokines.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

• Advise patients to discontinue mirikizumab and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.

• Advise patients that mirikizumab may lower the ability of their immune system to fight infections and to contact their healthcare provider immediately if they develop any symptoms of infection.

• Advise patients to contact their healthcare provider if they experience symptoms suggestive of tuberculosis (e.g., unexplained fever, cough, or difficulty breathing).

• Inform patients that mirikizumab may cause liver injury. Advise patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction (e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).

• Advise patients that vaccination with live vaccines is not recommended during mirikizumab treatment and immediately prior to or after treatment. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Instruct patients to inform their healthcare provider that they are taking mirikizumab prior to receiving a vaccination.

• Advise patients who are exposed to mirikizumab during pregnancy to contact Eli Lilly and Company.

• Instruct patients in preparation and administration of mirikizumab, including choosing anatomical sites for subcutaneous administration, and proper subcutaneous injection technique. Instruct patients in the technique of pen disposal. Instruct patients or caregivers to administer two 100 mg prefilled pens to achieve the full 200 mg dose of mirikizumab.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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