What type of medication is Aklief (trifarotene)?

Aklief (Trifarotene): A Topical Retinoid for Acne Treatment

Aklief (trifarotene) is a first-in-class, fourth-generation topical retinoid that selectively targets retinoic acid receptor-gamma (RAR-γ) for the treatment of acne vulgaris. 1, 2

Classification and Mechanism of Action

• Trifarotene is classified as a terphenyl acid derivative retinoid with selective activity for RAR-γ, which is the most common retinoic acid receptor isoform in the skin 3, 2
• As a retinoid, trifarotene works through an "antikeratinizing" effect that normalizes follicular keratinization, reduces hyperkeratosis, and has anti-inflammatory properties 4, 2
• Trifarotene acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces comedone formation 2
• The medication also inhibits inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1 2

FDA Approval and Formulation

• Trifarotene received its first global approval in the USA in October 2019 for the topical treatment of acne vulgaris in patients 9 years of age and older 1
• Aklief Cream contains 0.005% (50 mcg/g) trifarotene, a much lower concentration than other topical retinoids due to its high selectivity for RAR-γ 3, 2
• The formulation includes inactive ingredients such as allantoin, copolymer of acrylamide and sodium acryloyldimethyltaurate, cyclomethicone, ethanol, medium-chain triglycerides, phenoxyethanol, propylene glycol, and purified water 3

Clinical Applications

• Trifarotene is indicated for both facial and truncal acne, making it the first topical retinoid with rigorous clinical data supporting efficacy for acne on the trunk 5, 2
• The American Academy of Dermatology recommends topical retinoids like trifarotene as first-line therapy for acne treatment due to their comedolytic and anti-inflammatory properties 4
• Trifarotene can be used as monotherapy for mild acne or in combination with benzoyl peroxide for moderate acne 4
• For severe acne, trifarotene can be part of a combination regimen including oral antibiotics and benzoyl peroxide 4
• Emerging evidence suggests trifarotene may also improve acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH) 6

Advantages Over Other Retinoids

• Trifarotene is the only topical retinoid specifically approved for both facial and truncal acne treatment 5, 2
• Its selective targeting of RAR-γ allows for efficacy at a much lower concentration (0.005%) compared to other topical retinoids 3, 2
• Clinical trials have demonstrated good tolerability with the common retinoid-associated side effects being generally manageable 5, 6

Common Side Effects and Management

• Like other topical retinoids, trifarotene can cause local skin reactions including erythema, scaling, dryness, stinging/burning, and pruritus 5, 6
• Photosensitivity may occur, requiring patients to use sunscreen and minimize sun exposure 4
• To minimize irritation, patients can start with less frequent application (every other day) and gradually increase to daily use as tolerance develops 7
• Combining trifarotene with moisturizers can help reduce irritation while maintaining efficacy 7, 6

Precautions and Contraindications

• As with other retinoids, trifarotene should be used with caution during pregnancy 7
• The medication may cause initial worsening of acne before improvement is seen, typically within the first few weeks of treatment 7
• Patients should be advised that trifarotene may bleach clothing or bedding 4

Trifarotene represents an important advancement in acne therapy as the first topical retinoid specifically designed and approved for both facial and truncal acne, with a unique selective mechanism of action targeting RAR-γ receptors.