}

Abrocitinib

Immunosuppressants

Drug Overview

Abrocitinib (brand name Cibinqo) is an oral Janus kinase (JAK) inhibitor approved by the FDA for the treatment of moderate to severe atopic dermatitis. It targets the JAK1 pathway to reduce inflammation.

It is prescribed for adults and adolescents with atopic dermatitis that is not adequately controlled by topical therapies. By modulating key inflammatory signaling, it helps relieve itching, redness, and skin lesions.

Mechanistically, abrocitinib blocks the activity of JAK1 enzymes involved in the immune response, thereby decreasing the production of inflammatory cytokines and improving skin symptoms.

Relevant Genes and Their Roles

CYP2C19 is a liver enzyme that metabolizes many drugs, including abrocitinib, by chemically modifying them to facilitate removal from the body. Variations in the CYP2C19 gene can change how quickly the enzyme works.

Individuals inherit different versions (alleles) of CYP2C19. Some versions speed up drug breakdown, while others slow it down. These differences can alter drug levels in the blood, affecting both effectiveness and risk of side effects.

Impact of Genetics on Drug Response

CYP2C19 metabolizer status plays a key role in abrocitinib exposure: rapid or ultrarapid metabolizers clear the drug faster, potentially reducing efficacy, whereas poor metabolizers clear it more slowly, increasing systemic concentrations and the likelihood of adverse reactions.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid Metabolizer

  • Effect on drug levels: Lower than average concentrations due to faster clearance
  • Clinical consequence: Potential reduced efficacy of abrocitinib
  • Side effects: Possibly fewer side effects; data on frequency are limited

Normal Metabolizer

  • Effect on drug levels: Expected therapeutic concentrations
  • Clinical consequence: Standard efficacy and safety profile
  • Side effects: Side effects consistent with clinical trial data, typically mild to moderate

Intermediate Metabolizer

  • Effect on drug levels: Slightly increased concentrations compared to normal
  • Clinical consequence: May have increased exposure; monitor response
  • Side effects: Possible mild adverse reactions; frequency may be somewhat higher

Poor Metabolizer

  • Effect on drug levels: Significantly higher concentrations due to slow clearance
  • Clinical consequence: Increased risk of adverse reactions
  • Side effects: Higher risk of serious side effects; monitor and adjust dose

Indeterminate/Not Available

  • Effect on drug levels: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
  • Side effects: Monitor per usual clinical practice

Dosing Guidelines

The following dosing guidelines are based on the available FDA pharmacogenomic guidance for abrocitinib and CYP2C19 metabolizer status.

CYP2C19 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Ultrarapid Metabolizer Your body breaks down the medication abrocitinib very fast. As of now, there are no special instructions for people with this trait. Your doctor will guide you with the usual dosage and usage of this medicine. Abrocitinib – label recommended dosage and administration
Rapid Metabolizer Your body breaks down the medication abrocitinib quite quickly. Your doctor will follow the standard dose and administration instructions for this medication. Abrocitinib – label recommended dosage and administration
Normal Metabolizer Your body processes the drug abrocitinib normally. Standard dosing guidelines are recommended. Abrocitinib – label recommended dosage and administration
Intermediate Metabolizer Your body may process abrocitinib at a slightly slower rate. Your doctor will continue to follow the standard dosage instructions, but will closely monitor your response to the medication. Abrocitinib – label recommended dosage and administration
Poor Metabolizer Your body may process abrocitinib slower than expected, which could increase risk of side effects. Your doctor may reduce your dose to ensure the medication works well for you. Results in higher systemic concentrations and may result in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations.
Likely Intermediate Metabolizer Based on your genetic result, your body may process abrocitinib at a slower than average rate. However, there's no need for making changes to the usual dosage recommended on the label, according to these results. Abrocitinib – label recommended dosage and administration
Likely Poor Metabolizer Your body may not break down the drug abrocitinib as effectively, which could increase side effects. Your doctor may suggest changing your dosage to suit you better. Results in higher systemic concentrations and may result in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations.
Indeterminate Your genetic test result does not give a clear answer on how your body processes abrocitinib. Abrocitinib – label recommended dosage and administration
Not available Your genetic test result does not give a clear answer on how your body processes abrocitinib. Abrocitinib – label recommended dosage and administration

Alternative Treatment Options

The current FDA guidance does not specify alternative drugs or dosing adjustments beyond abrocitinib labeling. Always consult your healthcare provider for other treatment options if needed.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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