Background Behçet's Disease is a rare, chronic variable vessel vasculitis presenting with oral and genital aphthous lesions, a variety of skin symptoms, arthritis and depending on its severity with uveitis, CNS and GI symptoms. Most often used drugs are colchicine, corticosteroids, azathioprine and cyclosporine. TNF inhibitors are used off-label (only in Japan approved) in particular for patients with uveitis to prevent blindness. Usually given TNF inhibitors are infliximab and adalimumab. These monoclonal antibodies are large molecules and as such they do not penetrate well into tissues following systemic administration.
We explored the clinical effect of a single chain anti-TNF antibody fragment (DLX105) consisting of 246 amino acids (molecular weight: 26 kDa) for flaring mucocutaneous Behçet's Disease.
Objectives The primary objective of this study was the describe the pharmacokinetics of DLX105 after a single fixed dose in patients with Behçet's Disease. The exploratory objective was to explore the preliminary efficacy of a single fixed dose of DLX105 on mucocutaneous lesions in patients with Behçet's Disease.
Methods A total of 6 patients with flaring Behçet's Disease received a single dose of 10 mg/kg i.v. DLX105. The main inclusion criteria were: males and females aged 18 to 65, with flaring Behçet's Disease defined by the criteria of the "International Study Group for Behçet's Disease (ISBD)" with at least two oral ulcerations for at least 3 days prior to enrollment. Patients were allowed to be on colchicine or low dose corticosteroids (≤7,5 mg/d). After a dosing visit (Day1) all patients attended two follow-up visits (Day 5 and 8) and an end-of-study-visit (Day 15).
Results Each patient had oral lesions at baseline (mean 3.7 ulcers, SD 2) which rapidly and almost completely disappeared within one week (mean 1 ulcer, SD 1.3) and stayed improved even after 2 weeks (mean 1.5 ulcers, SD 1). Genital lesions in one patient also resolved. Two patients with erythema nodosum showed a prompt and complete disappearance of skin nodules after one week of treatment. The number of papulo-pustular skin lesions in 5 patients also rapidly declined (mean 14.3 at baseline, after one week 7.2). Arthralgia present in 3 patients resolved within one week of treatment. The ISBD questionnaire score (range 0–12) dropped from 4.3 to 3.3 within one week and to 3.0 within two weeks indicating a sustained response. There were no SAEs and adverse events were mild and disappeared within 2 weeks.
Conclusions These data suggest that DLX105 has a rapid and strong onset of action likely due to its unique property to penetrate effectively into inflamed tissues. The duration of the response is far longer than its serum pharmacokinetics with a half-life of roughly one day suggested. Thus, DLX105 is a strong development candidate to treat flaring mucocutaneous Behçet's Disease.
Disclosure of Interest T. Xenitidis Grant/research support from: Unrestricted grant from Delenex therapeutics, C. Berger: None declared, T. Jung: None declared, J. Henes Grant/research support from: Unrestricted grant from Delenex therapeutics, I. Koetter Grant/research support from: Unrestricted grant from Delenex therapeutics