What is Opzelura (ruxolitinib)?

What is Opzelura (Ruxolitinib)?

Opzelura (ruxolitinib) is a topical JAK1/JAK2 inhibitor FDA-approved for the treatment of mild to moderate atopic dermatitis in non-immunocompromised patients aged ≥12 years and for non-segmental vitiligo in patients aged ≥12 years. 1, 2

Mechanism of Action

Ruxolitinib works by selectively inhibiting Janus kinases (JAK) 1 and 2, which are intracellular tyrosine kinases that play critical roles in:

• Cytokine signaling pathways involved in inflammation
• Development and function of several immune cell types
• Signal transduction and activation of transcription (STAT) pathways

By blocking these pathways, Opzelura interrupts the cytokine cascades responsible for:

• In atopic dermatitis: Blocking IL-4, IL-13, IL-31, and TSLP cytokines that drive itching and inflammation 1
• In vitiligo: Reducing enhanced immune response and promoting development of new, healthy pigmented skin cells 2

Formulation and Administration

• Available as a 1.5% cream formulation for topical application
• Applied as a thin layer to affected areas twice daily
• For atopic dermatitis: Can be used on up to 20% body surface area (BSA) with no more than 60g per week for up to 8 weeks 1
• For vitiligo: Applied to depigmented areas to promote repigmentation 3

Clinical Efficacy

Atopic Dermatitis

• Phase III studies showed significant improvement in disease severity, pruritus, and sleep disturbance compared to vehicle cream when applied twice daily for 8 weeks 4
• Disease control was maintained for up to 44 weeks when applied as needed to active lesions 4
• In maximum-use trials, 94.6% of patients achieved ≥75% improvement in Eczema Area and Severity Index by day 56 5

Vitiligo

• First FDA-approved at-home treatment for non-segmental vitiligo 2
• Phase III TRuE-V1 and TRuE-V2 trials demonstrated significant facial and total body repigmentation compared to vehicle 3
• Efficacy was sustained in longer-term analyses up to 104 weeks of treatment 3

Safety Profile

• Generally well-tolerated with a safety profile similar to vehicle cream in short-term use 4

• Most common adverse events:

  • Application site reactions (acne, pruritus, exfoliation, redness, itching) 4, 3
  • Inflammation of throat and nasal passages
  • Headaches and fever 2

• Important safety considerations:

  • Carries boxed warnings in the US for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, although incidence was low with topical application 3
  • Mean steady-state plasma concentration is typically well below the level expected to affect bone marrow production of blood cells 5
  • No significant safety findings suggestive of systemic JAK inhibition were identified in clinical trials 4

Differences from Oral Ruxolitinib (Jakafi)

It's important to distinguish Opzelura (topical ruxolitinib) from Jakafi (oral ruxolitinib), which is approved for different indications:

• Oral ruxolitinib (Jakafi) is FDA-approved for:

  • Myelofibrosis
  • Polycythemia vera in patients who have had an inadequate response to hydroxyurea
  • Acute and chronic graft-versus-host disease 6

• Topical ruxolitinib (Opzelura) has a more favorable safety profile compared to oral formulations due to limited systemic absorption 2

Clinical Pearls

• Opzelura should not be used in immunocompromised patients
• Avoid use on more than 20% BSA for atopic dermatitis
• Treatment response in vitiligo may take time, with continued improvement observed over extended treatment periods
• Monitor for application site reactions, which are the most common adverse events
• The topical formulation has significantly lower systemic absorption compared to oral ruxolitinib, reducing risk of systemic adverse effects

Opzelura represents a significant advancement in dermatology as it offers targeted immunomodulation directly to affected skin areas while minimizing systemic exposure and associated risks.