Sirolimus (Rapamycin) Induced Mucosal Healing in Anti-Tumor Necrosis Factor Refractory Pediatric Ulcerative Colitis

Abstract

Sirolimus (rapamycin) has been sparsely reported in the treatment of pediatric ulcerative colitis (PUC). Mucosal healing has not been examined in responders to the drug. We describe a case of infliximab refractory PUC where rapamycin induced sustained clinical remission along with mucosal healing. We conclude that rapamycin should be positioned into the expanding treatment repertoire of PUC.

mTORC1 Activation In Presumed Classical Monocytes: Observed Correlates With Human Size Variation and Neuropsychiatric Disease

“…The association of mTORC1 activity with rapamycin response is consistent with the literature, specifically rapamycin's efficacy in treating tuberous sclerosis [24]. Rapamycin also has documented efficacy in a host of polygenetic autoimmune disorders, specifically in the prototype disorder lupus [25] and the case-specific disorder ulcerative colitis [26]. Its proximal mechanism of action may relate to biasing differentiation of naive T-cells towards the FoxP3+ T-regulatory and CD8+CD45R0+ memory subtypes dependent on fatty acid oxidation and reducing interleukin (IL)-4 and IL-17 production by CD3+CD4-CD8-double negative T-cells.…”

Sirolimus Use in Refractory Crohn's Disease

“…Sirolimus use in pediatric populations with IBD has included a 14 patient retrospective study reporting its use in patients with ulcerative colitis and CD as well as a recent case report with both noting improved mucosal healing and achieving clinical remission in the observed patients. 4,6 Current literature in adults is limited to a single case report describing sirolimus therapy in a middle-aged female with refractory ileocolonic CD, noting mucosal healing and biomarker improvement. 7 Similarly, our case series noted sirolimus therapy to coincide with symptomatic improvement in all patients, with CRP reduction noted in 3 of 3 patients tested.…”