Long-term Results of Low-dose Intravenous Ciclosporin for Acute
Long-term Results of Low-dose Intravenous Ciclosporin for Acute
Background: Intravenous ciclosporin for acute, severe colitis is usually administered in a dose of 4 mg/kg/day, with concurrent intravenous steroids. This is associated with considerable morbidity. We have been using a low-dose regimen, most commonly without concurrent steroids, for seven years, and present the outcome.
Methods: Records of all patients admitted for severe ulcerative colitis, treated by one physician over seven years, were reviewed.
Results: Thirty-one patients received low-dose intravenous ciclosporin (2 mg/kg/day) for a median 8 days. Eleven early patients received concurrent intravenous corticosteroids. Three patients had hypertension requiring dose reduction, one elevated creatinine and one elevated liver enzymes (all transient), and four experienced infection (two arm cellulitis, one perianal abscess, one post-operative wound infection). Twenty-four patients (77%) avoided urgent colectomy, and were discharged on oral ciclosporin and azathioprine. After a median 18 months (range 3-77), 14 patients (45% of total) avoided colectomy, of whom eight had flares responding to medical therapy and two had persistent, mildly active disease.
Conclusions: Low-dose intravenous ciclosporin (2 mg/kg/day), usually used as a monotherapy and followed by azathioprine, achieves similar long-term efficacy to higher dose ciclosporin combined with steroids in severe acute ulcerative colitis. Morbidity appears to be low.
Approximately 15% of patients with ulcerative colitis experience fulminant episodes requiring admission to hospital during the course of their illness. Forty percent of such patients will fail to achieve remission with intravenous corticosteroids. In the past decade, intravenous ciclosporin at a dose of 4 mg/kg/day, with concurrent intravenous steroids, has become an established therapy in severe steroid-resistant ulcerative colitis, sparing 60-90% of patients from urgent colectomy. Some responders to ciclosporin will ultimately relapse, but 30-50% will not require surgery during long-term follow-up, particularly if also established on azathioprine.
Use of ciclosporin is, however, associated with considerable morbidity. Serious complications such as Pneumcystis carinii pneumonia and seizures may occur in as many as 12% of patients in large series, and deaths have been reported. Less serious but nevertheless troubling side effects, including hypertension, liver and renal impairment, tremor, paraesthesiae and headache, occur in up to 50% of patients.
One strategy to lessen the adverse effects of therapy is to use ciclosporin as monotherapy, avoiding the morbidity associated with concurrent corticosteroids. A second approach to decreasing side effects is to reduce the dose of ciclosporin. Actis et al., using low-dose intravenous ciclosporin (2 mg/kg/day) in the acute phase of treatment, have reported short term outcomes that are comparable with those of high-dose therapy, and possibly with less toxicity. One randomized trial showed a similar acute response rate in 35 patients treated with low-dose intravenous ciclosporin when compared to 35 treated with a higher dose, although the difference between actual mean doses was modest (1.82 compared with 2.65 mg/kg/day). In another case series, an intermediate dose of ciclosporin (2.5 mg/kg/day) achieved similar response rates to those reported with higher doses.
We have been using a low-dose regimen of intravenous ciclosporin (2 mg/kg/day) routinely in patients admitted with acute, severe ulcerative colitis since 1996, in recent years without concurrent intravenous high-dose corticosteroids. Patients who have initially responded have been treated with azathioprine and commenced on oral ciclosporin prior to hospital discharge. In this study we report both short and long-term outcomes in these patients.
Background: Intravenous ciclosporin for acute, severe colitis is usually administered in a dose of 4 mg/kg/day, with concurrent intravenous steroids. This is associated with considerable morbidity. We have been using a low-dose regimen, most commonly without concurrent steroids, for seven years, and present the outcome.
Methods: Records of all patients admitted for severe ulcerative colitis, treated by one physician over seven years, were reviewed.
Results: Thirty-one patients received low-dose intravenous ciclosporin (2 mg/kg/day) for a median 8 days. Eleven early patients received concurrent intravenous corticosteroids. Three patients had hypertension requiring dose reduction, one elevated creatinine and one elevated liver enzymes (all transient), and four experienced infection (two arm cellulitis, one perianal abscess, one post-operative wound infection). Twenty-four patients (77%) avoided urgent colectomy, and were discharged on oral ciclosporin and azathioprine. After a median 18 months (range 3-77), 14 patients (45% of total) avoided colectomy, of whom eight had flares responding to medical therapy and two had persistent, mildly active disease.
Conclusions: Low-dose intravenous ciclosporin (2 mg/kg/day), usually used as a monotherapy and followed by azathioprine, achieves similar long-term efficacy to higher dose ciclosporin combined with steroids in severe acute ulcerative colitis. Morbidity appears to be low.
Approximately 15% of patients with ulcerative colitis experience fulminant episodes requiring admission to hospital during the course of their illness. Forty percent of such patients will fail to achieve remission with intravenous corticosteroids. In the past decade, intravenous ciclosporin at a dose of 4 mg/kg/day, with concurrent intravenous steroids, has become an established therapy in severe steroid-resistant ulcerative colitis, sparing 60-90% of patients from urgent colectomy. Some responders to ciclosporin will ultimately relapse, but 30-50% will not require surgery during long-term follow-up, particularly if also established on azathioprine.
Use of ciclosporin is, however, associated with considerable morbidity. Serious complications such as Pneumcystis carinii pneumonia and seizures may occur in as many as 12% of patients in large series, and deaths have been reported. Less serious but nevertheless troubling side effects, including hypertension, liver and renal impairment, tremor, paraesthesiae and headache, occur in up to 50% of patients.
One strategy to lessen the adverse effects of therapy is to use ciclosporin as monotherapy, avoiding the morbidity associated with concurrent corticosteroids. A second approach to decreasing side effects is to reduce the dose of ciclosporin. Actis et al., using low-dose intravenous ciclosporin (2 mg/kg/day) in the acute phase of treatment, have reported short term outcomes that are comparable with those of high-dose therapy, and possibly with less toxicity. One randomized trial showed a similar acute response rate in 35 patients treated with low-dose intravenous ciclosporin when compared to 35 treated with a higher dose, although the difference between actual mean doses was modest (1.82 compared with 2.65 mg/kg/day). In another case series, an intermediate dose of ciclosporin (2.5 mg/kg/day) achieved similar response rates to those reported with higher doses.
We have been using a low-dose regimen of intravenous ciclosporin (2 mg/kg/day) routinely in patients admitted with acute, severe ulcerative colitis since 1996, in recent years without concurrent intravenous high-dose corticosteroids. Patients who have initially responded have been treated with azathioprine and commenced on oral ciclosporin prior to hospital discharge. In this study we report both short and long-term outcomes in these patients.