Use of sirolimus (rapamycin) to treat refractory Crohn's disease

Massey, D. C. O.; Bredin, F.; Parkes, M
September 2008
Gut;Sep2008, Vol. 57 Issue 9, p1294
Academic Journal
We present the case of a 37-year-old woman with severe refractory colonic and perianal Crohns disease who had lost response to second-line, steroid-sparing treatments azathioprine, methotrexate and infliximab. For many such patients extensive surgery has often been considered the only option. New insights provided by the results of genomewide association scanning in Crohns disease highlight autophagy, a cellular process implicated in the clearance of intracellular bacteria, as a key process in Crohn's disease pathogeneses. Sirolimus (rapamycin) is a drug used to upregulate autophagy in cell culture in the laboratory, and in clinical practice to prevent rejection following organ transplantation due to independent immunosuppressive action. Our patient was treated with sirolimus for 6 months at a dose that maintained serum trough levels of 5 ng/ml. There was marked and sustained improvement in Crohn's disease symptoms with the Harvey-Bradshaw index falling from 13 to 3, in serum markers of inflammation (C-reactive protein fell from 79 to 2) and endoscopic appearance. This is the first reported case of the use of sirolimus to treat Crohn's disease.


Related Articles

  • Certolizumab Pegol: In Crohn's Disease.  // BioDrugs;2007, Vol. 21 Issue 3, p195 

    â–´ Certolizumab pegol is a pegylated humanized Fab' fragment of an anti-tumor necrosis factor-a (TNFa) monoclonal antibody, which binds with high affinity to both membrane-bound and soluble TNFa and demonstrates high neutralizing potency for these factors. â–´ The elimination half-life...

  • Inflammatory Bowel Disease.  // American Journal of Gastroenterology;Oct2011 Supplement, Vol. 106, pS432 

    The article presents abstracts on medical topics including the impact of population stratification on the link between nine significant single nucleotide polymorphisms (SNPs) and Crohn's Disease (CD), the efficacy and safety of the application of adalimumab in CD, and the influence of C-reactive...

  • Efficacy of Enteral Nutrition During Infliximab Maintenance Therapy in Patients with Crohn's Disease. Yamamoto, Takayuki; Shiraki, Manabu // Digestive Diseases & Sciences;Jun2013, Vol. 58 Issue 6, p1802 

    No abstract available.

  • Outcome Predictors for Thiopurine Maintenance Therapy in Patients with Crohn's Disease. Park, Jae; Cheon, Jae; Hong, Sung; Kim, Tae; Kim, Won // Digestive Diseases & Sciences;Jan2012, Vol. 57 Issue 1, p133 

    Background: Little is known about the factors that predict clinical relapse in Crohn's disease patients receiving thiopurine therapy to maintain remission. The objective of this study was, therefore, to investigate these factors. Methods: A total of 82 Crohn's disease patients who received their...

  • A phase II trial of temsirolimus in second-line metastatic urothelial cancer. Gerullis, H.; Eimer, C.; Ecke, T.; Georgas, E.; Freitas, C.; Kastenholz, S.; Arndt, C.; Heusch, C.; Otto, T. // Medical Oncology;Dec2012, Vol. 29 Issue 4, p2870 

    This phase II trial assessed temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), as second-line therapy in patients with metastatic transitional carcinoma of the urothelium (TCCU) after failure of platinum containing therapy. From June/2009 to June/2011, we enrolled 15 patients...

  • Updating progress in sarcoma therapy with mTOR inhibitors. Blay, J.-Y. // Annals of Oncology;Feb2011, Vol. 22 Issue 2, p280 

    Background: Sarcomas are a diverse group of difficult-to-treat connective tissue neoplasms. The mammalian target of rapamycin (mTOR) pathway has been identified as a therapeutic target in many sarcomas and this article reviews the role of this pathway and updates clinical data for the available...

  • Cotargeting survival signaling pathways in cancer. Grant, Steven // Journal of Clinical Investigation;Sep2008, Vol. 118 Issue 9, p3003 

    Mammalian target of rapamycin (mTOR) is a component of a signaling pathway (PTEN/PI3K/AKT) that is frequently dysregulated in cancer. However, its precise relationship to the MAPK cascade (Ras/Raf/MEK/ERK), another pathway often implicated in tumorigenesis, has not been well defined. Recent...

  • Certolizumab Pegol in Crohn's Disease.  // BioDrugs;2007, Vol. 21 Issue 3, p203 

    The article presents the author's view related to the efficacy of the anti-cancer drug Certolizumab Pegol in treating Crohn's Disease. Studies show that the drug is effective for induction and maintenance of remission in Crohn's disease. Certolizumab pegol will increase the options available for...

  • Ten Days vs. 14 days Antibiotic Therapy in Culture-Proven Neonatal Sepsis. Gathwala, Geeta; Sindwani, Arvind; Singh, Jagjit; Choudhry, Ojasvini; Chaudhary, Uma // Journal of Tropical Pediatrics;Dec2010, Vol. 56 Issue 6, p433 

    Background: There are no evidence-based guidelines for the treatment of neonatal sepsis although standard text books recommend 14 days of antibiotics for blood culture-proven neonatal sepsis. Objective: The present study compared the effectiveness of a 10-day course of antibiotic therapy with...


Read the Article


Sign out of this library

Other Topics