From the Guidelines
Tacrolimus is a viable rescue therapy option for patients with acute severe ulcerative colitis (ASUC) who have failed to respond to intravenous corticosteroids, with a recommended dosing regimen targeting trough levels of 10-15 ng/mL. According to the third European evidence-based consensus on diagnosis and management of ulcerative colitis 1, tacrolimus has shown significant benefit over placebo in patients with UC, including those with severe colitis. The study found that 67% of patients on tacrolimus adjusted to trough levels 10–15 ng/ml achieved a partial response, compared to 18% of patients on placebo.
Key points to consider when using tacrolimus as rescue therapy in ASUC include:
- Starting dose: 0.05 mg/kg/day divided into two doses
- Dose adjustments: based on trough blood levels
- Target trough levels: 10-15 ng/mL during the initial acute phase, then reduced to 5-10 ng/mL for maintenance
- Treatment duration: usually 3-6 months
- Clinical response: often seen within 1-2 weeks
- Common side effects: tremor, headache, hypertension, renal impairment, and increased risk of infections
- Monitoring: regular checks of tacrolimus blood levels, renal function, electrolytes, and blood pressure are essential
It is essential to note that tacrolimus works as a calcineurin inhibitor, suppressing T-cell activation and inflammatory cytokine production, thereby reducing intestinal inflammation 1. Patients should be transitioned to maintenance therapy with thiopurines or biologics once remission is achieved. Tacrolimus offers an alternative to cyclosporine and infliximab as rescue therapy, particularly valuable for patients with contraindications to anti-TNF agents or those who have previously failed these treatments.
From the Research
Tacrolimus as Rescue Therapy in Acute Severe Ulcerative Colitis
- Tacrolimus can be used as a rescue therapy for patients with acute severe ulcerative colitis (ASUC) who do not respond to intravenous corticosteroids 2, 3, 4, 5.
- The effectiveness of tacrolimus in inducing clinical response and preventing colectomy in patients with ASUC has been demonstrated in several studies 6.
- A systematic review and meta-analysis found that tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC 6.
- The choice of rescue therapy, including tacrolimus, depends on various factors such as experience, drug availability, and individual patient characteristics 3.
- Timely decision-making with rescue therapy or surgical treatment is critical to manage ASUC without compromising the health or safety of the patients 2, 3, 4, 5.
Key Findings
- Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio = 4.61,95% confidence interval = 2.09-10.17, p = 0.15 x 10(-3)) 6.
- Rates of clinical response at 1 and 3 months were 0.73 (95% CI = 0.64-0.81) and 0.76 (95% CI = 0.59-0.87), and colectomy-free rates remained high at 1,3,6, and 12 months 6.
- Adverse events were more frequent with tacrolimus compared with placebo, but there was no difference in severe adverse events 6.
Management of Acute Severe Ulcerative Colitis
- Intravenous corticosteroids remain the primary initial therapy for ASUC, although one-third of patients do not respond to treatment 2, 3, 4, 5.
- Rescue therapy with tacrolimus or other agents is indicated in patients who do not sufficiently respond to corticosteroids after 3-5 days 4.
- Timely colectomy should be performed if medical therapy fails to prevent critical complications 2, 3, 4, 5.