A pilot trial on safety and efficacy of erythrocyte-mediated steroid treatment in CF patients

BACKGROUND: Chronic neutrophil inflammation of the respiratory tract tissues plays a key role in the pathogenesis and in prognosis of cystic fibrosis (CF). It is evident that an anti-inflammatory therapy represents an important step in the treatment of CF patients. Corticosteroids and ibuprofen have been proven to slow down the impairment of the pulmonary function in CF patients but their use is limited by the frequency of adverse events. A novel strategy for delivering low doses of steroids for long periods through the infusion of autologous erythrocytes loaded with dexamethasone has been recently set up. A recent study suggested the feasibility of therapy with low doses of corticosteroids delivered through engineered erythrocytes in CF patients. This study presents a further analysis of safety and efficacy of this therapy. METHODS: The treatment group was not randomised and the assignment was based on the patient's consent. Patients entered the study if they had a forced expiratory volume in 1 second (FEV1) <70%, puberty development completed, pancreatic insufficiency, and chronic pulmonary infection requiring frequent cycles of intravenous antibiotic therapy. Patients were excluded if they underwent systemic corticosteriod therapy in the three months preceding the experimental treatment or were on therapy with non-steroidal anti inflammatory drugs (NASDs), or if they had liver CF disease, allergic bronchopulmonary aspergillosis, or positive tuberculin test. Controls were patients who followed a standard treatment, who fulfilled the enrolment criteria, and who were matched to the experimental group by gender, age, and severity of the disease. RESULTS: Nine patients in the experimental group received the treatment once a month for a period of 24 month. Patients did not develop diabetes, cataract, or hypertension, or other typical side effects of steroid treatment during the follow up period. There was a constant improvement of FEV1 in patients undergoing the experimental treatment compared to a gradual decrease of the same parameter in the standard therapy group (P = 0.04). The average of clinic and radiological indexes did not vary. The number of infective relapses that have required antibiotic intravenous therapy was not different in the two groups, although the average of these episodes was slightly higher in the experimental therapy group. CONCLUSION: Intraerythrocyte corticosteroid treatment may stabilize the respiratory function in CF patients but is often considered too invasive by patients. The results obtained by our study may help planning an experimental, controlled, randomised study. A sample size of 150 patients per group would be sufficient for demonstrating such a difference with a 95% confidence interval and a power of 90%.