What is the role of Rinvoq (upadacitinib) in treating moderate to severe eczema (atopic dermatitis)?

Role of Rinvoq (Upadacitinib) in Treating Moderate to Severe Eczema

Rinvoq (upadacitinib) is strongly recommended for adults with moderate to severe atopic dermatitis, but only after failure of other systemic therapies (including biologics) or when those therapies are inadvisable. 1

Placement in Treatment Algorithm

Upadacitinib is an FDA-approved JAK-1 inhibitor that serves as a second-line systemic therapy in the management of moderate-to-severe atopic dermatitis. The treatment algorithm for atopic dermatitis typically follows this progression:

1. First-line therapies:

   • Topical treatments (corticosteroids, calcineurin inhibitors)
   • Emollients and moisturizers
   • Trigger avoidance

2. Second-line therapies:

   • Phototherapy (narrowband UVB)
   • Biologics (dupilumab, tralokinumab)

3. Third-line therapies:

   • JAK inhibitors (upadacitinib, abrocitinib)
   • Traditional immunosuppressants (cyclosporine, methotrexate, azathioprine)

Efficacy and Evidence

Upadacitinib has demonstrated strong efficacy in treating moderate-to-severe atopic dermatitis:

• Achieves 75% improvement in Eczema Area and Severity Index (EASI75) in 71% of patients at 16 weeks 2
• Provides rapid and significant itch reduction as early as week 1 of treatment 3
• Shows superior efficacy compared to dupilumab in head-to-head trials, with 27.9% of patients achieving complete skin clearance (EASI100) versus 7.6% with dupilumab 2
• Maintains effectiveness in patients who previously had inadequate response to dupilumab and/or baricitinib 4

Dosing

The FDA-approved dose for atopic dermatitis is 15 mg or 30 mg once daily, with effectiveness observed in a dose-dependent manner 5.

Safety Considerations

Upadacitinib carries important safety warnings that must be carefully considered:

• Boxed warnings include:

  • Serious infections (including tuberculosis)
  • Increased mortality risk
  • Malignancy (higher rates of lymphomas and lung cancers)
  • Major adverse cardiovascular events
  • Thrombosis 6

• Common adverse events include:

  • Acneiform eruptions (21.3%)
  • Herpes simplex infections (12.8%)
  • Nausea (8.5%)
  • Airway infections (8.5%) 4

Patient Selection and Monitoring

Before initiating upadacitinib:

• Screen for latent tuberculosis
• Update immunizations
• Evaluate hepatic function
• Assess pregnancy status
• Check complete blood count 6

Avoid initiation or interrupt treatment if:

• Absolute lymphocyte count <500 cells/mm³
• Absolute neutrophil count <1000 cells/mm³
• Hemoglobin <8 g/dL 6

Clinical Pearls and Pitfalls

• Do not use as first-line therapy: Despite its efficacy, upadacitinib should only be used after failure of other systemic therapies due to its safety profile 1
• Avoid combination therapy: Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants 6
• Monitor for infections: Interrupt treatment if serious infection occurs until the infection is controlled 6
• Consider discontinuation: In real-world practice, about 29.8% of patients discontinue upadacitinib due to ineffectiveness, adverse events, or both 4

When to Consider Upadacitinib

Consider upadacitinib when:

1. Patient has moderate-to-severe atopic dermatitis
2. Disease is not adequately controlled with topical therapies
3. Patient has failed other systemic therapies (including biologics like dupilumab)
4. Other systemic therapies are inadvisable
5. Impact on quality of life is significant

Conclusion

Upadacitinib represents an important addition to the therapeutic armamentarium for moderate-to-severe atopic dermatitis, particularly for patients who have failed other systemic therapies. Its rapid onset of action and superior efficacy compared to biologics like dupilumab make it a valuable option, but its use must be balanced against its safety profile, which includes serious risks that require careful monitoring.