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

Abstract

Venous leg ulcers (VLUs) have higher tumor necrosis factor-α (TNF-α) levels compared with normal skin. Refractory VLUs of long duration have higher TNF-α 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-α 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-α 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-α staining score reductions (P = 0.02, R(2) = 0.999). VLU TNF-α level decrease 4 weeks post-adalimumab treatment correlated with wound healing.

Microbiome‐skin‐brain axis: A novel paradigm for cutaneous wounds

“…Although probiotic studies for treatment of human skin diseases are now underway, as yet none for chronic wounds are currently listed in the NIH Clinical Trials database . The successful preclinical studies demonstrating improved wound healing in animals treated with anti‐inflammatory agents have prompted a number of ongoing clinical trials with topical and systemic anti‐inflammatory agents as potential therapies for chronic wounds . These classes of agents could be further investigated as potential therapies to concurrently treat chronic wounds and the associated mood disorders.…”

“…Likewise, recombinant IL‐1RA improves wound healing in diabetic mice by downstream upregulation of CXCL10 . TNF‐inhibitors have also shown limited, yet promising, results, altering M1/M2 macrophage balance in the wound, and increasing wound collagen deposition . Findings on biomarkers of chronic wounds and their therapeutic targets are currently limited due to the small number of clinical studies, small sample sizes, and wide range of confounding variables contributing to the multifactorial nature of different types of chronic wounds.…”

Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization

“…Topical application of anti-TNF-α neutralizing antibodies blunts leukocyte recruitment and NF-κB activation, alters the balance between M1 and M2 macrophages, enhances matrix synthesis, and finally accelerates wound healing in the secretory leukocyte protease inhibitor (SLPI) null mouse model, which has age-related delayed human wound healing [58]. Topical application of infliximab and adalimumab, monoclonal antibodies of anti-TNF, is effective for patients with chronic ulcers [59,60].…”

Scarless wound healing: Transitioning from fetal research to regenerative healing

“…The majority of test subjects experienced improved wound closure within 8 weeks (Streit, Beleznay, & Braathen, 2006). In a separate non-controlled study, patients with chronic venous leg ulcers were treated with the TNFA inhibitor adalimumab (Fox et al, 2016). Several of the wounds demonstrated healing during the study period, and the degree of healing correlated with a reduction of TNF staining seen on immunohistochemical examination of wound biopsies.…”