Low-dose atovaquone for prophylaxis of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases: an open-label, multicentre, single-arm, phase II trial.

OBJECTIVES

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening complication that occurs in immunocompromised individuals, including patients with connective tissue diseases under glucocorticoid treatments. Trimethoprim-sulfamethoxazole (TMP-SMX) and atovaquone 1500 mg/d, the first and one of the second-line prophylactic options of PCP, are often difficult to continue the administration due to side effects or the cost. This trial aimed to investigate the efficacy and safety of low-dose atovaquone (750 mg/d) for prophylaxis of PCP in patients with connective tissue disease who started glucocorticoid treatments.

METHODS

This open-label, multicentre, single-arm, phase II trial included patients with connective tissue diseases who were scheduled to start or within 10 days from the initiation of 0.5 mg/kg/d or more of prednisolone or equivalent dose. All patients received low-dose atovaquone for 24 weeks. The primary endpoint was the incidence of PCP at 24 weeks, and adverse events were also assessed as secondary endpoints.

RESULTS

Fifty patients were assigned to receive low-dose atovaquone, and 45 were included in the primary analysis. Thirteen patients (28.9%) had comorbidities of lung diseases, and 33 (73.3%) received one or more immunosuppressants or biologics in addition to glucocorticoids during the trial period. No cases of PCP occurred up to 24 weeks. There were 7 nonserious and 2 serious adverse events, including 2 nonserious adverse events possibly related to low-dose atovaquone.

CONCLUSIONS

Results of this trial suggest that low-dose atovaquone has sufficient efficacy for the prophylaxis of PCP and a good safety profile in patients with connective tissue diseases under glucocorticoid treatments.