Introduction Calcineurin inhibitors (CI), most commonly ciclosporin, may be used as salvage therapy in patients with refractory moderate-severe ulcerative procto-colitis (UC), who would otherwise require surgery.1 However, use of CI may be limited by drug toxicity. For patients who have a good clinical response to ciclosporin but experience side effects, tacrolimus may be used as an alternative.2 We report our experience with CI in patients with moderate-severe UC whom either failed, or were intolerant of, thiopurines and as an alternative to surgery.
Methods NICE (January 2008) did not support the use of infliximab in patients with moderate-severe UC.3 Our patients were offered the choice of surgery or treatment with CI. Clinical response was assessed by AWH in clinic. If ciclosporin (4–6 mg/kg/day in two divided doses) led to a clinical response but caused intolerable side effects, tacrolimus (0.1 mg/kg/day in two divided doses) was offered as an alternative. Failure of therapy prompted referral for surgery.
Results 14 patients (8 female; mean age 38 [range 22–56] years) were treated with CI (13 ciclosporin, 1 tacrolimus). Ten of 14 (71%) patients had an initial clinical response to CI. Adverse effects were common (57%): nausea, paraesthesia, menstrual disturbance, maculopapular rash, hypertension (two patients) and renal dysfunction (one patient). Of the four patients who failed to respond to CI, three were referred for surgery and one patient is managed on mesalazine suppositories. A further four patients stopped treatment with CI due to adverse effects: two were referred for surgery and two were offered treatment with methotrexate. 6 (43%) of 14 patients responded successfully to CI and without side effects. 4 (30%) of these remain on CI: 3 on ciclosporin (mean duration of treatment 39 [range 19–71] months) and one patient on tacrolimus (duration of treatment 24 months); two patients stopped treatment with CI for reasons unrelated to efficacy or adverse effects (one to start a family and the other out of choice).
Conclusion CI should be considered as an alternative therapy for patients with refractory moderate-severely active UC who would otherwise require surgery. CI can be used safely and effectively in the presence of an established evidence-based protocol to ensure safe prescribing and monitoring for adverse side effects.
Competing interests None declared.
References 1. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Eng J Med 1994;330:1841–5.
2. Ogata H, Matsui T, Nakamura M, et al. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006;55:1255–62.
3. Ulcerative colitis (subacute manifestations)–Infliximab (TA140) NICE.
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