The Effect of Intranasal Niclosamide on Nasal Symptoms in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: Ear, nose, and throat (ENT) manifestations are common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There is an 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 hypothesized that intranasal niclosamide would reduce AAV-associated ENT symptoms. METHODS: PROTECT-V was a randomized, double-blind, placebo-controlled platform trial evaluating pre-exposure prophylaxis agents against COVID-19 infection. This subanalysis includes patients from a single center 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 32 (14 niclosamide; 18 placebo) patients, 11 (34%) were female; the median age was 69 (interquartile range [IQR] 59-75) years. Median prior AAV disease duration was 5.4 (IQR 1.9-13.1) years; 19 (59%) had active disease in the year before treatment. Median treatment exposure was 200 (IQR 109-251) days. During treatment, ENT symptoms were identified in 1 of 14 (7%) of the niclosamide group compared with 7 of 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 of 10 in the niclosamide group compared to 5 of 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 IL-6 and STAT3 pathway in AAV; intranasal niclosamide or other drug candidates in this pathway warrant further evaluation.