Targeted Therapy Using Intradermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
Condition: Lupus Erythematosus, Discoid; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Chronic Cutaneous
MeSH terms: Lupus Erythematosus, Systemic; Lupus Erythematosus, Discoid; Lupus Erythematosus, Cutaneous
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether Etanercept which is given through
      intradermal injection is effective in the treatment of discoid lupus erythematosus (DLE).

      The investigators also would like to develop new tests to measure skin inflammation by
      scanning the affected skin using optical coherence tomography (OCT), thermography and laser
      doppler imaging (LDI) and taking photographs of the rash (to be done before and after
      treatment). If the findings from these new tests are similar to the ones from taking a sample
      of skin (biopsy), then the latter (which is an invasive test) can be avoided.
    

Detailed description: 
      There is an unmet need for new therapies to control inflammation in discoid lupus
      erythematosus (DLE). A significant proportion of DLE patients (with or without systemic lupus
      erythematosus (SLE)) are resistant to conventional therapies and DLE may be exacerbated by B
      cell depletion therapy.There is no clinical guideline or algorithm on how to manage patients
      with DLE who have refractory disease to the first line agents, anti-malarials. If left
      untreated, uncontrolled inflammation will lead to permanent disfiguring and irreversible scar
      to the patient, thus pose a major cosmetic issue and significantly impair the quality of
      life.

      Targeted therapy based on immunopathogenesis is an attractive approach and tumour necrosis
      factor (TNF) is implicated in the pathogenesis of DLE. However, systemic administration of
      TNF blockers has been associated with induction of pathogenic autoantibodies that may render
      SLE worse or progression from DLE only to SLE. TNF blockers have been administered using the
      intra-dermal injection route in other TNF-mediated diseases and appear similarly safe and
      effective to systemic administration.

      Another issue is the problem with outcome measures as skin disease is particularly
      heterogenous and many instruments rely on subjective assessment which may be difficult even
      in the hands of experts.

      The TARGET-DLE trial will address these problems by: (i) administering a TNF blocker,
      etanercept using the intra-dermal route, which will provide local concentration to neutralise
      TNF in tissue while minimises the effect to systemic immunity and (ii) measuring tissue
      response using the existing outcome measure; the modified limited Score of Activity and
      Damage in DLE (SADDLE) as well as new objective measures such as skin biopsy, optical
      coherence tomography (OCT), thermography and laser Doppler imaging (LDI).

      Data from this study may be used to power a definitive randomised controlled trial should the
      primary end point be achieved.
    

Intervention name(s): Etanercept
Intervention type(s): Drug
Intervention description(s): Treatment with etanercept is intended for remission induction of DLE only and not for maintenance purpose.
Other intervention name(s): Enbrel
Intervention MeSH terms: Etanercept
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Discoid lupus erythematosus; Intradermal injection of etanercept