Cyclosporine in Ulcerative Colitis
Role as Rescue Therapy in Acute Severe UC
Cyclosporine is recommended as rescue therapy for patients with acute severe ulcerative colitis who fail to respond to intravenous corticosteroids by day 3, with equivalent efficacy to infliximab for avoiding short-term colectomy. 1
When to Initiate Cyclosporine
Start rescue therapy on day 3 of intravenous corticosteroid treatment if patients show inadequate response, as judged by validated scoring systems (Travis criteria, Oxford index, or Swedish index). 1
Patients requiring rescue therapy are those with ≥6 bloody bowel movements daily plus systemic toxicity markers (heart rate >90 bpm, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h) who remain unresponsive to IV methylprednisolone 60mg/24h or hydrocortisone 100mg four times daily. 1
Do not delay beyond day 7 of corticosteroid therapy, as prolonged ineffective medical treatment increases postoperative complication rates. 1
Dosing and Administration
Use intravenous cyclosporine at 2 mg/kg/day, which has equivalent efficacy to 4 mg/kg/day with fewer adverse events. 1
Continue IV cyclosporine for approximately 7-14 days before transitioning. 3
Bridging Strategy and Maintenance
Cyclosporine should be used as a bridge to thiopurine therapy (azathioprine or 6-mercaptopurine) in thiopurine-naïve patients, or to advanced biologic therapy in thiopurine-experienced patients. 1
In thiopurine-naïve patients: Bridge to azathioprine or 6-mercaptopurine for maintenance therapy, as this strategy can maintain remission in 37-46% of patients long-term. 4, 3
In thiopurine-experienced patients (those with prior inadequate response to appropriately dosed thiopurines with therapeutic TGN levels for >3 months): Do not use cyclosporine—choose infliximab instead, as the colectomy rate after cyclosporine in this population is 59%. 1
Comparative Efficacy
A prospective trial demonstrated equivalent short-term efficacy between cyclosporine and infliximab for rescue therapy in acute severe UC, with similar adverse event profiles. 1, 5
However, retrospective data suggest lower colectomy rates with infliximab compared to cyclosporine in some cohorts. 1
Cyclosporine induces remission in approximately 64-76% of patients initially, but without maintenance therapy, nearly half require colectomy within one year. 2, 3
Critical Contraindications and Precautions
Absolute contraindications: Toxic megacolon, severe hemorrhage, or perforation—these patients require immediate subtotal colectomy. 1
Monitor for nephrotoxicity and neurotoxicity, which are the primary serious adverse events, though most reverse after discontinuation. 2, 3
Ensure adequate thromboprophylaxis with low-molecular-weight heparin, as UC patients are at increased thrombotic risk. 1
Correct electrolyte abnormalities (particularly hypokalemia and hypomagnesemia, which can promote toxic dilatation) and maintain potassium supplementation of at least 60 mmol/day. 1
When Surgery is Preferred Over Cyclosporine
Patients who do not respond within 7 days of cyclosporine rescue therapy require subtotal colectomy and ileostomy. 1
Early surgical consultation is mandatory—multidisciplinary involvement with gastroenterologists, colorectal surgeons, and stoma therapists should occur from admission. 1
Delay in surgery increases postoperative complications; prolonged admission prior to surgery is a significant predictor of adverse surgical outcomes. 1
Role in Moderate-to-Severe Outpatient UC
Cyclosporine has no role in the outpatient management of moderate-to-severe UC. 1
For outpatients with moderate-to-severe disease unresponsive to aminosalicylates and corticosteroids, advanced therapies (anti-TNF agents, vedolizumab, JAK inhibitors, or anti-integrins) are recommended, not cyclosporine. 1
Cyclosporine is specifically reserved for hospitalized patients with acute severe disease refractory to IV corticosteroids. 1
Common Pitfalls to Avoid
Do not use oral cyclosporine for long-term maintenance in UC—the evidence does not support this approach, and toxicity risks outweigh benefits. 2, 4
Do not delay rescue therapy decision-making—assess response by day 3 and initiate rescue therapy rather than continuing ineffective corticosteroids beyond day 7. 1
Do not use cyclosporine monotherapy without a bridging plan—always have a strategy to transition to thiopurines or biologics for maintenance. 1
Exclude CMV colitis before initiating cyclosporine, as CMV infection is associated with steroid-refractory disease and requires specific antiviral treatment. 1