What is the role of dupilumab (Dupixent) in prurigo nodularis (PN) and itch related to interleukin-31 (IL-31)?

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Last updated: March 24, 2025 • View editorial policy

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From the Guidelines

Dupilumab is an effective treatment for prurigo nodularis (PN) and itch related to interleukin-31 (IL-31) signaling, with a standard regimen of 600 mg subcutaneously as an initial loading dose, followed by 300 mg every two weeks. The medication works by blocking the IL-4 receptor alpha subunit, which inhibits both IL-4 and IL-13 signaling pathways, and although it doesn't directly target IL-31, it reduces itch in PN by downregulating the inflammatory cascade that involves IL-31, a key cytokine in pruritus 1.

Key Points

  • Dupilumab has been shown to significantly reduce itch intensity within 12 weeks of treatment, with many patients experiencing improvement as early as 2-4 weeks 1.
  • The medication also reduces the number and size of PN lesions over time, improving quality of life for patients with PN.
  • Common side effects include injection site reactions, conjunctivitis, and, rarely, facial redness, highlighting the need for careful patient monitoring and management of ocular surface disorders 1.
  • Before starting treatment, patients should be screened for helminth infections and consider tuberculosis testing to minimize potential risks.

Management of Ocular Surface Disorders

  • For patients with mild, moderate, or severe dupilumab-related ocular surface disorders (DROSD), preservative-free ocular lubricants are recommended as first-line treatment 1.
  • Topical antihistamine eyedrops can be offered as a second-line treatment option in addition to ocular lubricants if symptoms persist 1.
  • Referral to ophthalmology is recommended for patients with severe DROSD or those who do not respond to topical treatment and lid hygiene, to assess the need for prompt intervention and potential withdrawal of dupilumab treatment 1.

Clinical Considerations

  • Dupilumab can be used concurrently with topical corticosteroids during the initial treatment phase to provide faster symptom relief while waiting for dupilumab's full effect to develop.
  • The safety profile of dupilumab has been shown to be excellent, with a low risk of serious adverse events, but careful monitoring and management of ocular surface disorders are essential to minimize potential risks 1.

From the FDA Drug Label

DUPIXENT is a prescription medicine used: to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies ... to treat adults with prurigo nodularis (PN) DUPIXENT works by blocking two proteins that contribute to a type of inflammation that plays a major role in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and chronic obstructive pulmonary disease

The role of dupilumab (Dupixent) in prurigo nodularis (PN) is to treat adults with this condition. There is no direct information in the label about the role of dupilumab in itch related to interleukin-31 (IL-31) 2.

From the Research

Role of Dupilumab in Prurigo Nodularis (PN)

  • Dupilumab has been shown to be effective in treating prurigo nodularis (PN), a chronic pruritic skin disease, with significant improvements in pruritus and skin inflammation 3, 4, 5, 6.
  • The treatment with dupilumab appears to be safe and well-tolerated, with most patients experiencing a good or excellent response to the treatment 3, 6.

Mechanism of Action

  • Dupilumab is a recombinant complete human monoclonal antibody that modulates the signaling of interleukin-4 and interleukin-13 pathways, which are involved in the development and perpetuation of PN and other type-2 inflammation diseases 3, 5.
  • The treatment with dupilumab has been shown to decrease serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and interleukin (IL)-22, whereas those of IL-13 and IL-31 remained unchanged 7.

Itch-Related Events

  • Dupilumab has been shown to attenuate itch and skin inflammation in patients with atopic dermatitis (AD) and PN, with significant improvements in pruritus numeric rating scale (p-NRS) scores and sleeplessness numeric rating scale (s-NRS) scores 7, 6.
  • Serum IL-31 levels have been positively correlated with the number of intraepidermal nerve fibers (IENFs) in AD patients, suggesting that IL-31 may play a role in the pathophysiology of itch in PN and AD 7.

Predictive Factors of Response

  • Time until patient perceived any improvement (Time_First) and time until patient reported absence of pruritus (Time_Final) have been identified as predictive factors of response to dupilumab treatment in PN patients 4.
  • Patients with atopic dermatitis (AD) have been shown to respond faster to dupilumab treatment than those without AD, with a more remarkable reduction in Investigator's Global Assessment (IGA) scores 6.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Research

Dupilumab as promising treatment for prurigo nodularis: current evidences.

The Journal of dermatological treatment, 2022

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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