Lipitor reduces colectomy rate in ulcerative colitis
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Lipitor may be a novel therapeutic option in patients with ulcerative colitis, according to study results published in Journal of the American Medical Informatics Association.
“Long-term atorvastatin (Lipitor) use is associated with reduced rate of colectomy in patients with UC,” Purvesh Khatri, PhD, from the Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University in California, told Healio Gastroenterology. “Our results also suggest that it may also be associated with lower rates of hospitalization and new steroid prescriptions.”
Khatri and colleagues identified an ulcerative colitis disease gene signature by conducting a multi-cohort analysis of 272 colon biopsy transcription samples from 11 public datasets. To identify potential drug targets, researchers compared the gene signature with in vitro transcriptomic profiles induced by 781 FDA-approved drugs. To determine the protective impact of predicted drugs on colectomy risk in patients with UC from the Stanford Research Repository (STARR) database and Optum Clinformatics DataMart, investigators modeled a retrospective cohort study designed after a target trial.
Among non-oncolytic FDA-approved therapies, results showed atorvastatin treatment had the highest inverse-association with the ulcerative colitis gene signature. Atorvastatin intake in both STARR (n = 827) and Optum (n = 7,821), correlated with a decreased risk for colectomy, a marker of treatment-refractory disease, compared with patients prescribed a comparator drug (STARR: HR = 0.47, P = .03; Optum: HR = 0.66, P = .03), regardless of age and length of atorvastatin treatment.
“All data used in our manuscript are retrospective cohorts,” Khatri told Healio Gastroenterology. “Therefore, the next step is to validate this finding in a cohort of prospectively enrolled patients. Further, our results suggest that the protective effect is also observed with other statins, but we did not have enough patients treated with other statins to derive a conclusion. Hence, one of the next steps is to understand whether the protective effect is atorvastatin-specific or general to all statins. The other issues to think through are the dose and duration patients with ulcerative colitis should be treated with atorvastatin or another statin.”
Khatri said if these findings are validated in a prospective cohort, this will move close to changing patient care.
Perspective
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Benjamin Cohen, MD, MAS
Bai et al. used a multi-cohort analysis approach to identify a strong gene signature for UC that, when compared against the profiles of FDA approved compounds, isolated atorvastatin as a potential therapy. Using a retrospective cohort design, the authors supported this finding by showing that atorvastatin use was associated with lower risk of colectomy. A prior study by Crockett et al. published in Inflammatory Bowel Diseases in 2012 suggested that statin use in ulcerative colitis was associated with a reduced rate of steroid use in an administrative claims database.
We have reached a therapeutic plateau with our currently available therapies for inflammatory bowel disease. Additionally, these therapies are limited by cost and potential for adverse effects, as well as mode of administration.
Bioinformatics offers the potential to identify new applications of existing therapies that may have benefits in IBD. Drug repositioning has been an effective strategy in other diseases such as Parkinson’s and colon cancer. It is important that we explore all avenues to improve our treatment of ulcerative colitis and Crohn’s disease. The potential of atorvastatin to be a new therapy, even as an adjunctive agent, is intriguing given its low cost and safety. However, findings such as these will need to be validated in prospective controlled trials as there are potentially confounding factors which may bias the findings in this retrospective study.
Reference:
Crockett SD, et al. Inflamm Bowel Dis. 2012;doi:10.1002/ibd.21822.
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