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47 Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus (TARGET-DLE): results from a proof-of-concept phase II trial
  1. Md Yuzaiful Md Yusof1,
  2. Miriam Wittmann1,
  3. Catherine Fernandez1,
  4. Duncan Wilson1,
  5. Sara Edward2,
  6. Giuseppina Abignano1,
  7. Adewonuola Alase1,
  8. Philip Laws2,
  9. Mark Goodfield1,
  10. Paul Emery1 and
  11. Edward Vital1
  1. 1University of Leeds
  2. 2Leeds Teaching Hospitals NHS Trust


Background A significant proportion of patients with discoid lupus erythematosus (DLE) are resistant to conventional therapies. Tumour necrosis factor (TNF) is pathogenic in DLE. A concern with systemic TNF-i administration is induction of pathogenic autoantibodies and flare of disease. This could be overcome using a low-dose intra-dermal injection, which may be sufficient to neutralise the TNF in lesions, without systemic TNF effects.

The objective of this trial was to assess the efficacy and safety of a novel route of administration of a TNF-i using a low dose intra-dermal injection of etanercept (ETN) for remission induction in DLE.

Methods A prospective single arm, Simons 2-stage minimax design with Hybrid adaptation, phase II open label trial was conducted in Leeds [NCT02656082]. Key inclusion criteria were i) adults aged 1880 y; ii)oneactive DLE lesion and iii) refractory to anti-malarials. One index lesion with the highest activity was treated with weekly intra-dermal injection of up to 10 mg ETN. The primary endpoint was 6 patients achieving the modified limited Score of Activity and Damage in DLE (ML-SADDLE) 20 response (defined as reduction 20% in total activity comprises erythema, induration and scaling from baseline) at Week 12 for a Phase 3 trial to be recommended. Secondary endpoints included change in objective outcome measures; lesional thermography and laser Doppler imaging.

Results All 25 DLE patients were recruited over 18 months (18 female, mean age 47±12 y, 6 had SLE, 9 had positive ANA and median (range) no. of previous systemic therapies was 5 (116) 17 patients completed the primary efficacy assessment [Did not attend Week 12 visit=1, early withdrawals=7 (personal choice=2, AE=2, worsening of DLE=1, non-compliance=1, pregnant=1)]. The primary endpoint was met with 13/25 (52%, 95% CI 3173) meeting the ML-SADDLE 20 in full-set analysis. The rates for ML-SADDLE 50 and 70 were 48% and 20% respectively. Key secondary endpoints were met (table 1). Fifty-one AEs (treatment-emergent=28, Grade 3/4=4) were recorded. There was no worsening of BILAG or SLEDAI in patients with SLE. Trough serum ETN levels were detected in 6/23 (26%).

Abstract 47 Table 1

Secondary Endpoints (per protocol; n=17)

Conclusions Intradermal injection of ETN substantially reduced clinical activity, met its primary, secondary endpoints and was tolerable in DLE patients who were refractory to anti-malarials and other systemic therapies. This drug warrants further development in multi-centre trials. Analyses of other imaging and histological biomarkers are ongoing and can help stratifying patients for response.

Funding Source(s): National Institute of Health Research

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