Anti-IL17A, Ixekizumab, for treatment-resistant chronic venous leg ulcers: A phase II randomised, double-blind, placebo-controlled pilot trial

Chronic venous leg ulcers cause significant morbidity in patients and the majority reoccur after resolution. The current standard of care, double layer compression, is not effective in all patients. Interleukin 17A (IL17) antagonist therapy has been shown to promote healing in murine models of chronic wounds. This has not previously been explored in humans. Therefore, we aim to undertake a phase II randomized, double-blinded, placebo-controlled pilot trial to assess whether Ixekizumab, an anti-IL17A therapy, is effective at reducing chronic venous ulcer size. In addition, to determine the feasibility and safety of undertaking a randomized control trial. Patients with a venous leg ulcer not responsive to 4 weeks of compression therapy were recruited. Participant were randomized to receive either Ixekizumab (80mg) or placebo injected subcutaneously every fortnight for 12 weeks while continuing standard of care. From 30 eligible, 4 patients consented, were enrolled and randomized. Initially, COVID-19 risk, medical history and distance from recruiting site were the main causes of exclusion or refusal to participate. All participants completed the 12-week treatment period. At completion, two participants in the Ixekizumab group reduced by >40% and one completely resolved their ulcer. Ulcers in the Ixekizumab group reduced by an average size of 955mm2 to 529mm2at baseline to final review respectively (p-value 0.12). The placebo group reduced in size by <5%.There were no adverse events related to the intervention. This pilot clinical trial investigated a novel treatment for chronic venous ulcers and showed IL17 inhibition does not impede and may improve chronic wound healing. It also showed a lack of major safety issues in using anti-IL17A therapy in this population. Moreover, the findings reinforce the feasibility of a larger trial to more accurately evaluate anti-inflammatory strategies in chronic wounds.