Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds

Abstract

The role of tumour necrosis factor-alpha (TNF-alpha) in wound healing is not clear. Elevated levels of TNF-alpha have been observed in fluids from chronic wounds and have been shown to decrease over time during the healing process. Therapeutic antibodies such as infliximab can inhibit TNF-alpha activity. In this case series, we applied infliximab topically to eight patients with chronic ulcers of more than 4-month durations. The ulcers had multifactorial aetiology, with chronic venous insufficiency being the most prominent factor. All the ulcers had failed to respond to any previous conventional treatment. Infliximab was applied repeatedly to ulcers either as a 10 mg/ml solution and covered with an adhesive sheet or as a gel formulation (0.45, 1, or 4.5 mg/g) under a hydrofiber dressing/adhesive sheet. Improvement was assessed by measuring the percentage of change in the ulcer surface area. Seven of the eight patients (12 of 14 ulcers) responded to treatment with infliximab. After 4 weeks of treatment, surface area was reduced by more than 50% in 6 of the 14 treated ulcers. Within 8 weeks, five ulcers completely healed, while another four were reduced by more than 75% in size. Chronic, therapy-resistant leg ulcers responded well to repeated topical administration of a solution or a gel containing the TNF-alpha antibody, infliximab. Randomised controlled studies should be conducted to further evaluate the effect of topical infliximab on chronic wound healing.

Figure 1

Case 1: (A) ulcer before treatment with infliximab solution, (B) ulcer 3 weeks after first application of infliximab solution, (C) ulcer 12 weeks after first infliximab application (3 weeks after second application of solution).

Figure 2

Case 2: (A) ulcerative lesions before treatment with infliximab gel, (B) ulcer 3 weeks after infliximab (two applications of the gel).

Figure 3

Case 1: (A) positive reaction to mouse anti‐infliximab antibody deposits around dermal vessel in direct immunofluorescence staining, indicating infliximab presence in the ulcer tissue, (B) positive reaction along basal membrane, indicating infliximab in the tissue.