*2.2. Participants*

This study enrolled patients over the age of 18 years, with clinically confirmed HHT su ffering from epistaxis (more than 30 min during the 6 weeks prior to the time of inclusion justified by completed follow-up grids), and who had not undergone nasal surgery in the 6 weeks prior to inclusion. We did not include women who were pregnan<sup>t</sup> or those likely to become so during the study, or patients with known hypersensitivity to macrolides in general, to tacrolimus or to any of the excipients, or patients who had incompletely filled in the nosebleed grids, or patients with an inherited skin barrier, or with CYP3A4 inhibitor treatment (erythromycin, itraconazole, ketoconazole, and diltiazem), or patients with ongoing immunosuppressive treatment, or with known and symptomatic immune deficiency.

#### *2.3. Patient Information and Follow-Up*

Patients were informed and recruited during a standard consultation with the ENT doctor or doctor responsible in the reference center or skill center for HHT, and informed of the study and the need to complete nosebleed grids for ENT monitoring for the 6 weeks prior to the start of the treatment. Patients were included during a consultation at the reference center or skill center for HHT and the treatment was prescribed during the same consultation.

The follow-up consisted of 2 phone calls on days 15 and 31 (i.e., 14 and 30 days after the beginning of the treatment) in order to collect information regarding tolerance and observance, and in visits (with medical and ENT consultations) at the end of the 6 weeks of treatment, and at 6 weeks after the end of the treatment.

#### *2.4. Study End Points*

The main outcome was the percentage of patients experiencing an improvement in their nosebleeds. An improvement was defined as a 30% reduction in the total duration of nosebleeds over the 6 weeks following treatment, compared with the duration of the nosebleeds in the 6 weeks before the treatment.

Secondary outcomes were total duration of nosebleeds, number of nosebleeds, and number of red blood cell transfusions before, during, and after treatment, progress in the scores obtained in the SF36 quality of life questionnaire and in the ESS (Epistaxis Severity Score) using data from the specific questionnaire and biological e fficacy criteria (hemoglobin and serum ferritin). All were recorded before treatment and at 6 and 12 weeks after the end of the treatment.
