Dupilumab: paradoxical reactions

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Our experience with dupilumab in AD

• dupilumab available in The Netherlands since Q4 2017
• ≥1 systemic immunosuppressant before dupi (≥2 in 70%)
• n=287 AD patients started dupilumab at Erasmus MC (8/2020)

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Effectiveness in Daily practice

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Dupilumab in daily practice

Effectiveness:

• comparable to clinical trials

Side effects:

• dupilumab induced ocular disease (conjunctivitis)
• paradoxical ‘head and neck dermatitis’
• less frequent side effect (arthralgia)

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Incidence of eye complaints (9-62%)

• Erasmus MC & Amsterdam UMC
  • de Wijs et al, BJD 2019: 59/95 patients: eye complaints (62%)
  • Bosma et al., JAAD 2020: 46/221 patients: severe AE (21%)
• Faiz et al. JAAD 2019 (France): 84/241 (38%)
• Ruiz-Villaverde et al. Derm. Ther. 2019 (Spain): 6/70 (9%)
• Olesen et al., JEADV 2019 (Denmark): 7/43 (18%)

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Treatment of conjunctivitis

Dermatologist:
Rx/

• artificial tears + anti-histamine eye drops from start dupi treatment
• topical tacrolimus ointment peri-ocular (NB ante noctum)
  
• consider early referral to opthalmologist:
  • tacrolimus 0,03% eye ointment
  • steroids

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Case series of ‘paradoxical head and neck erythema’

• 7 adult AD patients
• symptoms started 10-39 weeks after start dupilumab treatment
• sharply demarcated erythema in head/neck region
• different from their pre-existing eczema (eg. burning sensation, little scaling)

• NB: treatment satisfaction rated by patients at time of biopsy was still high: 9 on a 10-point scale

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• Malassezia furfur associated “head and neck dermatitis”
• contactallergy
• site-specific failure
• drug induced photosensitivity
• dupilumab induced inflammatory response

• NB both clinically and histopathologically heterogeneous

• Treatment?

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Rare side effects

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Take home

• dupilumab induced ocular disease more frequent in daily practice
  • consider early ophthalmology referral and prophylactic treatment

• paradoxical head and neck dermatitis
  • jury is still out on its pathogenesis and treatment

• dupilumab may possibly induce various forms of arthropathy/enthesitis/tendinopathy
  • daily practice registries (eg. TREAT)

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Ask questions to Dirk Jan HIJNEN:

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Conflict of interest :

Investigator for Abbvie, Astrazeneca, Galderma, LEO pharma, Lilly,
MedImmune, Novartis, Sanofi/Regeneron, UCB

Consultancies for Regeneron/Sanofi, LEO pharma, MedImmune, Novartis,
Incyte, Janssen, Pfizer