Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.

Background: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment.

Objectives: To investigate the efficacy and safety of fumagillin in a real-life setting.

Methods: As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints.

Results: From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented.

Conclusions: E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.