Erythrocytes-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis: a randomized, double-blind Sham-controlled study

Background: Efficacy of erythrocyte-mediated delivery of dexamethasone 21-phosphate in patients with steroid-dependent ulcerative colitis.

Methods: Thirty-seven patients with steroid-dependent ulcerative colitis were randomized to infusions of dexamethasone 21-phosphate encapsulated into autologous erythrocytes (n = 19) or to sham infusions (n = 18). Each infusion was given monthly for 6 months. The primary endpoint was the proportion of patients able to discontinue oral corticosteroids during treatment while maintaining clinical remission or stable disease. Secondary endpoint was the proportion of patients with disappearance of steroid-related adverse events.

Results: At each infusion, a mean of 9.8 ± 4.6 mg dexamethasone 21-phosphate was administered at each infusion, which allowed steady-state plasma levels of 8 ng/mL for the following 28 days. Thirteen patients in the dexamethasone 21-phosphate group and 4 sham-treated patients attained the primary outcome of the study, i.e., maintaining a stable condition despite oral Steroids withdrawal (P = 0.008). In the remaining patients (6 and 15 in the 2 experimental groups, respectively), the treatment was prematurely withdrawn because of clinical deterioration while tapering oral Steroids. At endoscopy, mucosal healing was ascertained in 4 patients and 1 patient of the 2 experimental groups, respectively (P = 0.339). At inclusion, 14 and 13 patients in the 2 experimental groups complained of steroid-related adverse events; at end of the treatment, events were still present in 5 and 13 patients, respectively (P = 0.008).

Conclusions: In patients with steroid-dependent ulcerative colitis, 6-month therapy with low dose of dexamethasone 21-phosphate allowed the withdrawal of oral Steroids and the reversal of steroid-related adverse events in most patients while maintaining clinical remission (ClinicalTrials.gov number, NCT01171807).