Tacrolimus or infliximab for severe ulcerative colitis: short-term and long-term data from a retrospective observational study

Abstract

Objective: Treatment of severe ulcerative colitis (UC) is challenging. Although the efficacy of tacrolimus (TAC) and infliximab (IFX) have been evaluated in patients with severe UC, the safety and efficacy levels of sequential therapies (TAC→IFX/IFX→TAC) in these patients remain unclear. The aim of this study was to assess short-term and long-term outcomes in patients with severe UC treated with TAC and IFX.

Methods: From October 2001 to February 2014, 29 patients with consecutive severe UC treated with TAC or IFX were retrospectively evaluated. Median follow-up duration was 27 months (range 0.5-118 months). The primary end point was short-term outcomes at 8 weeks after induction of TAC (TAC group, n=22) or IFX (IFX group, n=7). The secondary end point included long-term outcomes and colectomy-free survival. The clinical response was evaluated based on a partial Mayo score.

Results: The clinical remission (CR) rate at 8 weeks in the TAC and IFX groups was 63.6% and 71.4%, respectively. In 13 of the 29 patients (10 in the TAC group, 3 in the IFX group), sequential therapies were used in their clinical courses. In 9 of these 13 patients (6 in the TAC group, 3 in the IFX group), CR was achieved and maintained by sequential therapies. Overall cumulative colectomy-free survival was 79.3% at 118 months.

Conclusions: TAC and IFX had similar effects on remission induction in patients with severely active UC. Sequential therapies could rescue patients with UC who failed initial treatment with TAC or IFX. In clinical practice, sequential therapies might be deliberately performed.

Keywords: IBD CLINICAL; INFLAMMATORY BOWEL DISEASE; ULCERATIVE COLITIS.

Figure 1

Short-term and long-term outcomes of the 29 patients with severe ulcerative colitis (UC). Short-term outcomes: 14 of 22 patients in the tacrolimus (TAC) group and 5 of 7 patients in the infliximab (IFX) group achieved a clinical remission (CR) at 8 weeks after initiating TAC or IFX. Two patients in the TAC group were refractory to TAC and required sequential therapy. Two patients in the IFX group were refractory to IFX and one could achieve a CR after switching to TAC. The remaining one resulted in colectomy without switching to TAC. The CR rate at 8 weeks in the TAC and IFX groups was 63.6% and 71.4%, respectively. Long-term outcomes: In the TAC group, of 14 patients who achieved a CR at 8 weeks after initiating TAC, 11 patients could maintain a CR and 3 flared-up. A total of nine patients could not achieve and maintain a CR with TAC. Six of the nine patients could achieve a CR by sequential therapy, and the remaining three resulted in colectomy (one patient within 6 months). Two patients who required sequential therapy within 8 weeks after initiating TAC resulted in colectomy within 6 months after initiating TAC. In the IFX group, of four patients who achieved a CR at 8 weeks after initiating IFX, three could maintain a CR and one flared-up. A total of two patients could not achieve and maintain a CR with IFX and they could achieve a CR by sequential therapy. One patient who achieved a CR by sequential therapy within 8 weeks after initiating IFX could maintain a CR. *Reveals the patient who resulted in colectomy within 6 months after initiating TAC or IFX.

Figure 2

(A) Proportion of patients who avoided colectomy (n=23). The overall cumulative colectomy-free survival was estimated to be 79.3% at 118 months, based on Kaplan-Meier survival analysis. (B) Proportion of patients who avoided colectomy (n=17 in the tacrolimus (TAC) group and n=6 in the infliximab (IFX) group). The cumulative colectomy-free survival was estimated to be 77.3% at 118 months in the TAC group (solid line) and 85.7% at 79 months in the IFX group (dashed line) (p=0.704).