However, the long-term data for cyclosporine have not been encouraging. In a retrospective cohort of 76 patients with severe UC who received IV or oral cyclosporine, 56 patients (74%) achieved initial remission.¹³ At 12 months, 65% of patients who had originally achieved remission on cyclosporine had had at least one UC flare. Moreover, at 84 months 58% of patients had gone on to colectomy (see Figure 2). In subgroup analysis, azathioprine (given for maintenance after induction of remission with cyclosporine) did not affect the rates of relapse or colectomy.

Therefore, cyclosporine is an effective rescue therapy for hospitalized UC patients refractory to steroids, but this effect is short-lived and the longterm results are disappointing. Additionally, cyclosporine is not without risks and serious adverse events, such as seizures, renal failure, and opportunistic infection, have been reported.

Is Tacrolimus an Alternative Option?
Tacrolimus, like cyclosporine, works by inhibition of interleukin (IL)-2 synthesis and release. Its role in refractory UC is not as well studied. In a study of moderate to severe steroid-refractory UC, 60 patients were randomized to high-trough FK concentrations, low-trough, or placebo.¹⁴ After two weeks, 13 of 19 patients (68.4%) in the high-trough (10–15ng/ml) groups had a partial response—defined as a four-point or greater drop in disease activity index (DAI)—compared with a placebo response of only two of 20 (10%; p<0.001). Mucosal healing was also achieved in 78.9% of the high-trough group. Notably, patients in the low-trough (5–10ng/ml) group did not have a clinically significant response. Also, patients in this study were felt to be less severe, being ‘refractory’ to <30mg oral doses of prednisone. In a longer open study of IV or oral tacrolimus, patients were followed for a mean of 16 months.¹⁵ Thirteen of 38 patients (34%) with refractory UC went into complete remission at one month, while the two-year colectomy rate was 50%.

In general, the jury on tacrolimus in severe UC is still out. Its short-term efficacy may be similar to that of cyclosporine, with potentially less toxicity; however, long-term data are lacking. The inflammatory bowel disease (IBD) community has been slow to embrace this option.

Are There Any New Medications Available?
At present, there are no new medications available. Visilizumab, a humanized anti-CD3 monoclonal antibody, initially showed promise;¹⁶ however, it was not found to be more effective than placebo in a phase III trial. Basiliximab and daclizumab, both monoclonal antibodies blocking the IL-2 receptor alpha-chain (CD25) on activated T cells, have both had mixed results, and neither drug is available.^17,18 MLN02, a monocolonal antibody that blocks α4β7 integrin, has shown efficacy in a phase II study of patients with active UC,19 and is currently being tested in a phase III trial.