mirikizumab

Action and Spectrum

Actions and Spectrum: 

Actions 

mirikizumab’s primary action is to inhibit IL-23, which helps regulate the production of other pro-inflammatory cytokines, including IL-17 and IL-22. By inhibiting IL-23, mirikizumab reduces the inflammatory response mediated by these cytokines.  

Spectrum 

mirikizumab has shown clinical efficacy in treating moderate to severe plaque psoriasis, with studies demonstrating significant improvement in skin clearance, disease severity reduction, and quality of life. It has shown superiority over placebo and comparability to other biologic therapies for psoriasis.

Drug Interaction

Adverse Reaction

Frequency defined

Infections of the upper respiratory tract (8-14%)

Headache (4%)

Rashes (4%)

Pain in joints (2-7%)

Reactions at the site of injections (9%)

Infections due to herpes virus (2%)

Hypersensivity (0.4%)

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions

• Pruritis or mucocutaneous erythema due to infusion
• Live vaccines should not be administered in patients receiving mirikizumab treatment
• Do not administer mirikizumab in patients suffering with tuberculosis

Comorbidities:

Hepatotoxicity as reported in a case during clinical trials

Pregnancy / Lactation

Pregnancy consideration:

US FDA pregnancy category: Not assigned

Lactation:

Data insufficiency

Pregnancy category:

Category A: Studies that were well-controlled and met expectations revealed no risk to the foetus `in either the first or second trimester.

Category B: There were a lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

mirikizumab selectively binds to the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor. This binding inhibits the downstream signaling pathway of IL-23, thereby reducing the production of pro-inflammatory cytokines, such as IL-17 and IL-22. By inhibiting IL-23, mirikizumab modulates the immune response and suppresses inflammation. 

Pharmacodynamics: 

By blocking IL-23, mirikizumab helps reduce the production of pro-inflammatory cytokines, particularly IL-17 and IL-22. IL-17 is involved in the recruitment and activation of immune cells, while IL-22 contributes to tissue inflammation and damage. Inhibition of these cytokines helps modulate the immune response and reduce inflammation. 

Pharmacokinetics: 

Absorption 

Absorption

When administered through subcutaneous route, bioavailability was noted as 44% with peak plasma time to be 5days.

99.7mcg/ml and 10.1mcg/ml are the peak plasma concentrations when administered through IV and SC routes respectively.

538 mcg⋅day/mL and 160 mcg⋅day/mL are the values of AUC when administered through IV and SC routes respectively.

Distribution 

mirikizumab is distributed throughout the body via the bloodstream. As a monoclonal antibody, it undergoes protein degradation and catabolism like endogenous antibodies. 

Volume of distribution: 4.83L

Metabolism 

mirikizumab is primarily metabolized through protein degradation and catabolism. 

Elimination and Excretion 

The drug is excreted in the urine.

Clearance: 0.0229 L/hr

Half-life: 9.3 days

Adminstartion

Administration: 

Intravenous administration

Give the IV infusion over a minimum of thirty minutes.

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

The minimum 30-minute infusion period must be added to the time needed to flush the IV line.

Subcutaneous administration

Subcutaneous injection sites include the back of the upper arm, the thigh, and the abdomen.

Always inject in a different area.

Avoid injecting into areas of skin that are indurated, erythematous, bruised, or tender.

Does not contain preservatives, so throw away any product that is not used.

Never reuse.

Patient Information Leaflet

Patient information leaflet

Generic Name: mirikizumab

Why do we use mirikizumab?

mirikizumab is a first-in-class drug used in the treatment of severe ulcerative colitis. Adult patients with moderately to severely active ulcerative colitis who have not responded well to, have lost response to, or are intolerant to biologics or conventional therapy may benefit from treatment with mirikizumab