Gender May Influence the Immunosuppressive Actions of Prednisone in Young Patients With Inflammatory Bowel Disease

Abstract

Although the use of glucocorticoids (GC) is well established, the therapeutic response to these agents often shows important interindividual differences, in particular among young patients with inflammatory bowel diseases (IBD). Currently, GC resistance or dependence cannot be predicted by clinical or laboratory findings. The aim of this study was to investigate the association of gender and age with GC efficacy and with the expression of Glucocorticoid-Induced Leucine Zipper (GILZ). One hundred thirty patients (mean age at enrolment 12.6 years, 53 Crohn’s disease, 70 males) were enrolled in this retrospective study. IBD patients with active disease despite prednisone at a daily dose of up to 2 mg/kg over a period of 4 weeks were defined as steroid resistant. Patients who initially responded but relapsed upon dose reduction were considered steroid-dependent. Total RNA was extracted from biopsies of 14 patients (9 males) and the levels of GILZ mRNA were evaluated by real-time PCR. Association between clinical response to prednisone and the considered demographic variables was evaluated using logistic regression models. After 4 weeks of treatment, 112 patients were responders to prednisone and 18 were resistant; at this time-point, resistant patients were older than responders (p=0.032). After 12 weeks, 42, 71 and 12 patients were sensitive, dependent and resistant respectively; at this time-point, females were more prone than males to develop prednisone dependence vs a good response (p=0.028) while age had no effect. Age was associated with response both at 4 and 12 weeks in the subgroups of females: resistant patients were older than sensitive ones at 4 weeks (p=0.02). Likewise, at 12 weeks of therapy, dependent patients resulted older than sensitive ones (p=0.05). No association of age with prednisone response was found in males. In a subgroup of 14 patients (5 females), GILZ mRNA expression in intestinal biopsies was higher in males (p=0.0031). Patients with unfavorable response (7) presented lower GILZ expression at disease onset in comparison to the responder group (p=0.017). Older females with IBD have a higher incidence of prednisone unfavorable response and reduced intestinal expression of the GC pharmacodynamic marker GILZ.