Cyclosporine in the treatment of severe attack of ulcerative colitis: a systematic review.
BACKGROUND
Intravenous steroid therapy is the standard treatment in severe attacks of ulcerative colitis (UC), but 20% to 60% of patients fail to respond and require colectomy. Cyclosporine (CyA) has shown efficacy in steroid failures and could avoid surgery, but controversy remains.


OBJECTIVE
The objective of this study was to conduct a systematic review to evaluate the effectiveness and safety of CyA in inducing remission in patients with a severe attack of UC.


METHODS
We did a systematic review using Cochrane methodology, including data from published (in English, French, Spanish or German) clinical trials done in adults using intravenous or oral CyA in UC. Data on efficacy are obtained from controlled and observational clinical trials, and for safety issues case reports are also considered.


RESULTS
31 studies were identified which met the inclusion criteria, 22 (18 uncontrolled, 4 controlled) with intravenous CyA, and 9 (all uncontrolled) using oral CyA. Only 4 controlled trials (one in abstract form) are available, and only one compares CyA to placebo. However, efficacy results are very consistent in these 4 trials, and very similar to those in observational studies. CyA achieves remission in 91,4% and 71.4% of patients in controlled and uncontrolled studies using intravenous route, and in 71,2% using oral route. Two mg/kg/day seems so efficacious and safer as previous standard 4 mg/kg/day dose. Minor side effects are rather common but do not seriously limit therapy. Severe side effects, specially infections, are uncommon but clinically relevant with several deaths reported.


CONCLUSIONS
CyA (intravenous, 2 mg/kg/day) constitutes an efficacious and relatively safe alternative in the treatment of severe, steroid-refractory, attack of UC. To optimize treatment, the correct selection of patients, a standardized protocol and clinical surveillance are recommended.
García-López
S
S
Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Zaragoza, Spain. sgarcial@meditex.es
Gomollón-García
F
F
Pérez-Gisbert
J
J
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D018849:Controlled Clinical Trials as Topic; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004198:Disease Susceptibility; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000209:etiology; D007262:Infusions, Intravenous; D012107:Research Design; D012640:Seizures / Q000139:chemically induced; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine