Adalimumab treatment leads to reduction of tissue tumor necrosis factor-alpha correlated with venous leg ulcer improvement: a pilot study

Venous leg ulcers (VLUs) have higher tumor necrosis factor-alpha (TNF-alpha) levels compared with normal skin. Refractory VLUs of long duration have higher TNF-alpha levels compared with VLUs of shorter duration. As up to 75% of VLUs fail to heal with standard care, we sought to evaluate the role of anti-TNF-alpha therapy for patients with refractory VLUs. Evaluable data were obtained in four of five subjects with recalcitrant VLUs treated with 80 mg of subcutaneous adalimumab at week 0 and with 40 mg at week 2 along with compression therapy and were followed-up for 6 weeks. Wound biopsies taken at weeks 0 and 4 were stained with anti-TNF-alpha antibodies. Average 4-week percent wound size reduction was 20.5%+/- 6.4%. Two patients had wound size reduction more than 25%, and their percent wound size reduction correlated to percent TNF-alpha staining score reductions (P=0.02, R-2 = 0.999). VLU TNF-alpha level decrease 4 weeks post-adalimumab treatment correlated with wound healing.