Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis

Patients were considered responder if, at the EoS, one of the following occurred:

• Disease remission (Powell Tuck index ≤ 3 or CDAI < 150) and withdrawal of oral steroids therapy from at least the second treatment procedure;
• Disease marked improvement vs basal conditions (at least 5 point decrease in Powell Tuck or 150 point decrease in CDAI score) and withdrawal of oral steroids therapy from at least the second treatment procedure.

The Powell-Tuck index was calculated by adding the subscores given by 7 items. A total score < 10 indicated a mild activity of the UC, and a total score >14 a severe one. The higher the score the worse the outcome.

Crohn Disease Activity Index (CDAI) was a tool that combines subjective parameters, with objectives parameters. The score given to each parameter was inserted in an algorithm which provided the final Index value. A moderate CD showed a CDAI score between 220 and 450, while a CDAI > 450 was an activity index indicating a severe disease.

Blood levels of endogenous cortisol were determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient. As steroids suppress ACTH production resulting in lowering cortisol levels, the assessment of this parameter was intended to investigate the ability of the dexamethasone intra-erythrocytes administration in minimising this steroid adverse effect.

In child, from 1 to 16 years, the total serum cortisol reference range is 5-23 mcg/dL at 8 am, and 3-13 mcg/dL at 4 pm.

The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. To perform the test, anticoagulated blood is traditionally placed in an upright tube (Westergren tube) and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour. ESR was evaluated as supportive data for the assessment of the intestinal disease severity. It was determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient.

ESR normal values in blood were from 0 to 20 mm/hour. Higher values are considered abnormal both in adults and in children. For ESR values > 100 mm/hour, there is a high probability that an underlying cause would be found upon investigation.

CRP is a protein produced by the liver. A C-reactive protein test measures the level of C-reactive protein (CRP) in a blood sample. Normal levels of blood C-reactive protein are low (0.3 to 1.0 mg/L). In case of inflammation liver releases more CRP into your bloodstream: results equal to or greater than 8 mg/L or 10 mg/L are considered high. High levels of CRP may indicate a serious health condition that causes inflammation.

C-reactive protein (CRP) was determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient.

Inflammation parameters (CRP) were evaluated as supportive data for the assessment of the intestinal disease severity.

C-reactive protein was measured in milligrams per liter (mg/L). Results equal to or greater than 8 mg/L or 10 mg/L were considered high.

The Baron score was an endoscopic grading system for ulcerative colitis. Four grades are defined (0-3) by the Baron score according to the severity of macroscopic inflammation of the rectal mucosal appearances at rigid sigmoidoscopy: 0 = normal mucosa (ramifying vascular pattern clearly visible, no spontaneous bleeding, no bleeding to light touch);

• = abnormal mucosa but non-haemorrhagic appearances between scores 0 and 2;
• = moderately haemorrhagic (bleeding to light touch, but no spontaneous bleeding seen ahead of the instrument on initial inspection); 3= severely haemorrhagic (spontaneous bleeding seen ahead of instrument at initial inspection and bleeds to light touch).

The higher the score the worst the outcome. Due to the nature of the score, its assessment was limited to patients suffering from UC, only. (CD or UC steroid-dependant patients were planned to receive the study treatment procedure every 30 days for a total of 6 administrations)

At each access to the clinic (except at the baseline visit one), patients were questioned and/or examined for evidence of adverse events. An adverse event was defined as any untoward medical occurrence or unfavourable and unintended sign in a subject administered a pharmaceutical product, biologic (at any dose), or medical device, whether or not considered related to the use of that product. This includes the onset of new illness and the exacerbation of pre-existing conditions.

Steroid related adverse events were investigated to assess the ability of the therapeutic approach under study in reducing the occurrence or entity of steroid adverse effects.