Treatment of nosebleeds in Osler-Weber-Rendu disease (OWRD) is a therapeutic challenge. Intranasal anti-angiogenic sprays are a promising solution, requiring scientific validation, leading us to conduct the present study.

The main objective was to determine the minimum effective dose of bevacizumab by intranasal spray to treat epistaxis in OWRD: i.e., the dose resulting in≥50% reduction in the number of nosebleeds at 1 month of treatment compared to the month prior to inclusion for 60% of patients. The secondary objectives were to assess treatment efficacy at 3 and 6 months and progression in the number and impact of nosebleeds, and to document pharmacokinetics.

The study, named EROSB (treatment of epistaxis in patients with OWRD using a bevacizumab intranasal spray), under the French Hospitals Clinical Research Program (PHRC-I 2013), was selected by the Inter-regional Clinical Research and Innovation Group (GIRCI). It was a phase I/II prospective single-blind study based on 10 cohorts of 3 patients each, using the Continual Reassessment Method (CRM) to determine the minimum effective dose of bevacizumab.

Due to difficulties in recruiting enough patients, the study was stopped after inclusion of 15 subjects. The CRM method identified 64mg as the minimum effective dose. However, this result is not interpretable due to the small number of subjects.

The EROSB study did not succeed in identifying a minimum effective dose of bevacizumab, administered as intranasal spray that could reduce the number of nosebleeds compared to the month prior to inclusion. However, the initial results indicated almost no systemic passage of the substance.