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Saito et al. present a retrospective study conducted at a single tertiary referral centre over a period of 75 months with the aim of identifying predictive factors of response to intravenous ciclosporin in the setting of acute, severe ulcerative colitis (UC).[1] An acute, severe attack of UC will affect 25% of patients at some point during their disease course,[2] and 20% of first attacks of UC are ‘acute severe’ in nature.[3]

Patients presenting with acute severe UC failing to respond to intravenous corticosteroids at day 3–5 should be considered for rescue medical therapy with either ciclosporin or infliximab, with the aim of avoiding colectomy. Although there are predictive indices of response to corticosteroids,[4-6] predictive factors of response to ciclosporin are less well established.[7-10]

The study included 52 patients and stepwise multiple logistic analysis identified 4 predictive factors of response to intravenous ciclosporin; age at hospitalisation, difference in total protein between days 1 and 3, platelet count on day 1, and Lichtiger score on day 3. The former two parameters have been identified as predictive factors by previous studies.[6, 8, 9] The authors use these factors to propose a novel calculation formula and a decision tree analysis, which predicts colectomy with an accuracy of 90.4%, positive predictive value of 72.2% and negative predictive value of 100%.

Most patients included in the study had disease refractory to other agents including one patient previously treated with tacrolimus and two patients having received infliximab induction therapy. These treatments were stopped 4 weeks prior to ciclosporin administration. A further cohort of 29 patients had received 2–10 sessions of leucocytapheresis, which was discontinued 2–14 days before treatment with ciclosporin. Additionally, a significant proportion of patients had co-existing infection with 19 patients (36.5%) being diagnosed with cytomegalovirus reactivation and four patients (7.7%) found to have clostridial infection after starting ciclosporin.

Allowing for these factors, the study outcomes and proposed calculation formula and decision tree are interesting, and may prove useful in earlier and accurate clinical decision-making in the treatment of steroid-refractory acute severe UC.

Acknowledgement

  1. Top of page
  2. Acknowledgement
  3. References

Declaration of personal interests: Dr Hart has been on advisory boards for Abbott, MSD, Shire and Atlantic Pharmaceuticals, and has received research grants from Abbott and MSD. Declaration of funding interests: None.

References

  1. Top of page
  2. Acknowledgement
  3. References
  • 1
    Saito K, Katsuno T, Nakagawa T, et al. Predictive factors of response to intravenous ciclosporin in severe ulcerative colitis: the development of a novel prediction formula. Aliment Pharmacol Ther 2012; 36: 74454.
  • 2
    Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohns Colitis 2010; 4: 4317.
  • 3
    Edwards FC, Truelove SC. The course and prognosis of ulcerative colitis. Gut 1963; 4: 299315.
  • 4
    Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis. Gut 1996; 38: 90510.
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    Lindgren SC, Flood LM, Kilander AF, et al. Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis. Eur J Gastroenterol Hepatol 1998; 10: 8315.
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    Ho GT, Mowat C, Goddard CJ, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Aliment Pharmacol Ther 2004; 19: 107987.
  • 7
    Rowe FA, Walker JH, Karp LC, et al. Factors predictive of response to cyclosporintreatment for severe, steroid-resistant ulcerative colitis. Am J Gastroenterol 2000; 95: 20008.
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  • 8
    Cacheux W, Seksik P, Lemann M, et al. Predictive factors of response to cyclosporine in steroid-refractory ulcerative colitis. Am J Gastroenterol 2008; 103: 63742.
    Direct Link:
  • 9
    Aceituno M, Garcia-Planella E, Heredia C, et al. Steroid-refractory ulcerative colitis: predictive factors of response to cyclosporine and validation in an independent cohort. Inflamm Bowel Dis 2008; 14: 34752.
  • 10
    Huaman Rios JW, Casellas Jorda F, Malagelada Benapres JR, et al. Predictive factors of poor response to intravenous cyclosporine in steroid-refractory ulcerative colitis. Rev Esp Enferm Dig 2009; 101: 16371.