Sirolimus Use in Refractory Crohn’s Disease: A Case Series
AIBD 2023
Background:
The treatment options for patients with inflammatory bowel disease (IBD) are constantly evolving but there remain patients who do not respond to available therapies. Pediatric case series show the potential benefit of sirolimus therapy in refractory Crohn’s disease (CD), however limited data exists in adult patients. As such, we aimed to identify and characterize treatment outcomes in adult patients with CD initiated on sirolimus therapy for refractory CD.
Methods:
We performed a retrospective chart review at a tertiary care academic center between 1999 and 2023 to identify patients with IBD who received systemic sirolimus therapy for a primary indication of IBD. Manual verification of treatment was performed, with exclusion of patients receiving sirolimus for a non-IBD related diagnosis. Patients with a history of solid organ or bone marrow transplant were excluded. Demographic and medical data was collected. Data pertaining to IBD symptoms was completed through comprehensive chart review, with attention to self-reported changes in bowel habits, imaging, endoscopic data, and inflammatory biomarkers.
Results:
After exclusion and manual verification, we identified 4 patients (75% female, 100% Caucasian) aged 36-52 with CD who were treated with sirolimus for a primary indication of refractory CD. Patients had been treated with a median of 7 IBD-targeted therapies prior to sirolimus addition. Median sirolimus treatment duration was 524.5 days (IQR 68.5 – 1013.5 days). Of the 4 patients, 1 reported symptomatic improvement following sirolimus initiation, with noted improvement in abdominal pain along with reduction of bowel movements from 4 to 1 per day. No patients underwent treatment escalation while on sirolimus, with 3 of 4 patients being able to discontinue or reduce IBD-directed therapy. In terms of objective data, of the 3 patients with available C-reactive protein, all demonstrated a decrease following sirolimus initiation. Although endoscopic data was not consistently available, magnetic resonance enterography before and after treatment initiation demonstrated continued inflammation following sirolimus therapy. Sirolimus discontinuation occurred in all 4 patients due to adverse effects, including poor wound healing (2/4), refractory lower-extremity edema (2/4), and rash (1/4). In patient #3 and #4, sirolimus discontinuation occurred within 90 days due to dermatologic adverse effects.
Conclusions:
There have been studies in pediatric populations investigating the use of sirolimus in the treatment of refractory IBD. This case series presented 4 patients with CD who received sirolimus therapy for a primary indication of refractory CD. All patients had failed treatment with at least 6 other IBD-therapies. Our results reveal 1 of 4 patients reporting symptomatic improvement and whilst treatment escalation was not required, imaging measures of inflammation remained equivocal. Furthermore, all 4 patients required sirolimus discontinuation due to adverse effects. With minimal data currently available for use of sirolimus therapy in adults with refractory IBD, our findings suggest that its role may be limited by treatment-derived adverse effects. Further large-scale studies are needed to investigate the efficiency of sirolimus therapy in refractory IBD, with particular attention to treatment-limiting adverse effects.
