Objective Ear, nose and throat (ENT) manifestations are common in ANCA-associated vasculitis (AAV). There is unmet need for drugs to target these manifestations. Granuloma formation is characteristic of proteinase 3 (PR3)-AAV. In a zebrafish model, niclosamide inhibits PR3-induced granuloma formation. We hypothesised that intranasal niclosamide would reduce AAV-associated ENT symptoms. Methods PROTECT-V was a randomised, double-blind, placebo-controlled platform trial evaluating pre-exposure prophylaxis agents against COVID-19 infection. This sub-analysis includes patients from a single centre, with AAV, enrolled into the intranasal niclosamide arm. Clinical data were retrospectively collected for nine months before, during, and nine months after treatment. Researchers were blinded to treatment allocation. Results Of thirty-two (14 niclosamide; 18 placebo) patients, 11 (34%) were female; median age was 69 years (IQR 59-75). Median prior AAV disease duration was 5.4 years (IQR 1.9-13.1); 19 (59%) had active disease in the year prior to treatment. Median treatment exposure was 200 days (IQR 109-251). During treatment, ENT symptoms were identified in 1/14 (7%) of the niclosamide group compared with 7/18 (39%) of the placebo group (p = 0.04). No significant difference between groups was found in the nine months before or after treatment. Among PR3-ANCA-positive patients, 0/10 in the niclosamide group compared to 5/9 (56%) in the placebo group had ENT symptoms during treatment. Conclusion These data are a signal of potential clinical effect on ENT manifestations in AAV. They support a role for the IL6/STAT3 pathway in AAV; intranasal niclosamide or other drug candidates in this pathway warrant further evaluation.
Rona M. Smith (Thu,) studied this question.
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