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PTU-041 The use of cyclosporin a in acute severe ulcerative colitis: long-term outcomes
  1. L M Sharkey,
  2. F Bredin,
  3. A Nightingale,
  4. M Parkes
  1. Department of Gastroenterology, Addenbrookes Hospital, Cambridge, UK

Abstract

Introduction Cyclosporin A (CyA), a potent suppressor of T lymphocyte reponses, has been used to treat steroid-refractory acute flares of ulcerative colitis (UC) since the early 1990s as an alternative to colectomy. We present the Cambridge data regarding response rates andlong-term colectomy-free survival following use of CyA in this context.

Methods From our inflammatory bowel disease database we extracted details of all patients receiving CyA for UC between January 2000 and July 2009. 44 patients had received CyA, 37 for acute flares refractory to intravenous corticosteroid therapy. Hospital records were unavailable for two patients and two received this treatment twice, hence 37 episodes of CyA use in 35 patients were analysed.

Results 24 patients were male; aged 17–72 years. On admission 20 patients were on prednisolone (10–60 mg); three were established on immunomodulator therapy (five others had started <3 weeks prior to admission) and seven were on no treatment. CyA was started a median of 8 days after admission with most patients (31/37) receiving CyA orally from outset at a starting dose of 4.5–8.3 mg/kg daily (the patient receiving 4.5 mg/kg was pregnant). Doses were adjusted to achieve a level of 150–250 μg/l. The other six received intravenous CyA at 2–5 mg/kg (5/6 were treated before 2004), and were changed to oral CyA 2–8 days after starting. Of the 35 patients who received CyA for acute UC, 15 have undergone colectomy during median follow-up of 46 months. 11/15 surgeries were carried out due to lack of response in the acute phase after mean 6.1 days (range 2–12) of CyA. 20/24 patients who responded and were discharged on CyA have not required colectomy. The other four patients underwent colectomy 3–8 months post discharge. All patients were monitored by our IBD nurses, with weekly drug levels while on CyA. 15 side effects in 12 patients included headache (11%), paraesthesia and hypertension (8.5%) each. The latter, as well as renal impairment (5.7%) were treated with dose reduction. 5.7% of patients complained of tremors and one patient (2.8%) developed neutropaenia on combination CyA and azathioprine. As per our protocol, 84.6% (22/26 episodes) were started on a thiopurine at a mean of 6.8 weeks post-discharge from hospital (range 0–34 weeks) once the oral prednisolone dose was below 15 mg.

Conclusion Most UC patients requiring CyA received this orally with good tolerability and safety. Of patients who responded in the acute setting and were discharged on cyclosporine 83% have avoided colectomy. We attribute this success to close patient monitoring by our IBD nurses, and careful management of the wean over from CyA to azathioprine. Our data suggest that in those who respond CyA does not simply “delay the inevitable colectomy”.

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