244 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 Md Yuzaiful 1 , Md Yusof 1 , Miriam Wittmann 1 , Catherine Fernandez 2 , Duncan Wilson 2 , Sara Edward 3 , Giuseppina Abignano 1 , Adewonuola Alase 1 , Linda Sharples 4 , Philip Laws 5 , Mark Goodfield 5 , Edward M Vital 1 and Paul Emery 1 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UNITED KINGDOM, 2 Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UNITED KINGDOM, 3 Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, UNITED KINGDOM, 4 Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UNITED KINGDOM, and 5 Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, UNITED KINGDOM 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-blockade is induction of pathogenic autoantibodies and flare of lupus. This could be overcome using a novel route of drug delivery; intra-dermal injection without the systemic TNF effects. The study objectives were to assess efficacy and safety of a low dose intra- dermal injection of etanercept (ETN) for remission induction in DLE. Methods: A prospective single arm, Simon’s 2-stage minimax design, phase II open label trial was conducted in Leeds [NCT02656082]. Inclusion criteria were adults, 1 active DLE lesion and refractory to anti-malarials. One most symptomatic lesion was treated with weekly intra-dermal injection of up to 10mg ETN. The primary endpoint was 6/25 patients meeting the modified limited score of activity and damage in DLE (ML-SADDLE) 20 response (defined as reduction 20% in total activity from baseline) at week 12 for a Phase III trial to be recommended. Secondary endpoints included change in lesional thermography and laser Doppler imaging. Results: All 25 DLE patients were recruited over 18 months (18 female, mean age 47  12y, 6 had SLE, 9 had positive ANA and median (range) number of previous systemic therapies was 5 (1-16). 17 patients completed the primary efficacy assessment. The primary endpoint was met with 13/25 (52%, 95% CI 31-73) meeting the ML-SADDLE 20 in the full-set analysis. The rates for ML-SADDLE 50 and 70 were 48% and 20% respectively. Key secondary endpoints were met (Table 1). 51 AEs (treatment-emergent¼29, Grade 3/4¼4) were recorded. There was no worsening of BILAG or SLEDAI in patients with SLE. Trough serum ETN levels were detected in 6/23 (26%). Conclusion: In this first-in-disease study, a low dose intra-dermal injection of ETN substantially reduced clinical activity, met its primary and key secondary endpoints including patient-reported outcomes and objective measures. This therapy was tolerable and no major safety signals were observed. The results support further development of therapy in multi-centre trials. Analyses of other imaging and histological biomarkers are ongoing and can help stratifying patients for response. 244 TABLE 1: Results for secondary endpoints (per protocol; n ¼ 17) Endpoint Pre- Treament Post- treatment P-Value Physician VAS, mean (SD) mm 53.1 (16) 23.2 (20) <0.001 Patient VAS, mean (SD) mm 56.9 (28) 29.7 (28) 0.001 DLQI, mean (SD) 11.4 (7) 6.5 (6) <0.001 Laser Doppler Imaging, mean (SD) perfusion unit 495.1 (224) 376.2 (223) 0.018 Infrared thermography, mean (SD), ºCelcius 1.92 (1.17) 1.08 (1.05) 0.005 Disclosures: M. Md Yusof: None. M. Wittmann: None. C. Fernandez: None. D. Wilson: None. S. Edward: None. G. Abignano: None. A. Alase: None. L. Sharples: None. P. Laws: None. M. Goodfield: None. E. Vital: Grants/research support; EMV has received honoraria and research grant support from Roche, GSK POSTER VIEWING_III Thursday 2 May 2019 iii143 Downloaded from https://academic.oup.com/rheumatology/article-abstract/58/Supplement_3/kez107.060/5444360 by guest on 03 June 2020