Late Breaking Abstract - Benralizumab reduces eosinophils and ANCA in sputum in EGPA

<bold>Introduction:</bold> Benralizumab (30mg subcutaneous Q4W) is noninferior to mepolizumab (300mg sc Q4W) to induce clinical remission in patients with refractory EGPA (PMID: 38393328). <bold>Aims:</bold> We evaluated if treatment arms were associated with eosinophil reduction and ANCA in sputum in the randomized, double-blind, head-to-head MANDARA trial (<ext-link>NCT04157348</ext-link>). <bold>Methods:</bold> In a mechanistic sub-study (n=16) of the MANDARA trial, n=7 patients received benralizumab (52±11years, 57% female) and, n=9 received mepolizumab (58±16years, 78% female). Eosinophils, eosinophil activity (eosinophil peroxidase, EPX), T1/T2 cytokines and ANCA were assessed in blood and sputum pre- and post-treatment (PMID: 30179583). <bold>Results:</bold> Benralizumab reduced sputum eosinophils to <2.3% in 6/7 (86%) patients compared to mepolizumab (6/9, 66%) (χ2, P<0.01), but did not significantly reduce sputum EPX. At baseline, spANCA in both arms were comparable (mepo:4/9, 44%; benra: 3/7, 43%; only one sero-positive). Post-treatment, benralizumab significantly reduced spANCA levels compared to mepolizumab (P<0.05), with 2/7 (28%) remaining spANCA⁺. By comparison, there was an increase in the proportion of patients with spANCA on mepolizumab from baseline (6/9, 67%). Increase in spANCA correlated with spEPX (rho=0.65; P=0.01). The two patients on benralizumab who remained spANCA⁺ had elevated spEPX and ACQ-6≥1.5 at the time-point of sampling, despite having achieved clinical remission. Reduction of T2 cytokines was comparable in both arms. However, an increase in spIL-17A post-mepolizumab (P<0.05) was noted that correlated with an increase in spANCA. <bold>Conclusions:</bold> Benralizumab has a greater effect on reducing sputum eosinophils and ANCA levels in EGPA compared to mepolizumab.