Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors

Abstract

Abstract. Calcineurin inhibitors (CNIs) such as cyclosporin A (CSA) and tacrolimus (FK506) are efficacious in patients with steroid-refractory or steroid-dependent ulcerative colitis (UC). We retrospectively investigated patients with refractory UC treated with CNIs to elucidate the prognostic factors for a colectomy. Data from 59 patients (35 men and 24 women) were analyzed. CSA and FK506 were administered by intravenous infusion and peroral administration, respectively. The efficacy of the CNIs was assessed using Seo's complex integrated disease activity index. Categorical data analyses were also conducted. The results revealed that the response rates for CSA and FK506 were similar (CSA, 66.6%; FK506, 63.6%). However, oral FK506 had a slower onset of action than intravenous CSA. The risk factors for CNI non-responsiveness were: i) more than 10,000 mg of prednisolone used prior to CNI treatment; and ii) positivity for cytomegalovirus antigenemia (C7-HRP). The factors affecting the rate of colectomy were: i) CNI non-responsiveness; ii) more than 10,000 mg of prednisolone used prior to the initiation of CNI treatment; and iii) positivity for C7-HRP. The addition of azathioprine (AZA) following CNI treatment significantly reduced the incidence of colectomy. Our results revealed the prognostic factors affecting the efficacy of CNI therapy and the need for colectomy in patients with refractory UC. Importantly, some of these factors may be obtained prior to or shortly following the start of CNI treatment. Furthermore, AZA is an important agent for averting colectomy once a patient responds to CNIs.

Prognostic factors affecting early colectomy in patients with moderate to severe ulcerative colitis treated with calcineurin inhibitors

“…The significant factors predicting early colectomy were as follows: i) disease severity, ii) immunomodulator-naïve history, iii) lower serum hematocrit, iv) lower serum albumin levels and v) lower O-PNI scores. Conversely, the significant factors predicting the overall colectomy risk were i) C7-HRP positivity and ii) >10,000 mg prednisolone used prior to the initiation of CNI treatment; these results were concordant with those of our previous report (20). In accordance with these results, previous studies demonstrated that disease severity, the use of immunomodulators, and hematocrit levels can affect the rate of colectomy in UC (17,29).…”

“…The aim of the present study was to determine the prognostic factors for early colectomy following comparison with the results of our previous report (20), which would demonstrate the factors affecting the rate of colectomy at 1 year as well as the overall colectomy rate.…”

“…We have previously reported that the factors affecting the rate of colectomy at 1 year and the overall colectomy rate were i) CNI non-responsiveness, ii) >10,000 mg prednisolone used prior to the initiation of CNI treatment and iii) positivity for C7-HRP (20). However, the response to CNIs may not be obvious prior to the start of CNI administration.…”

“…Our previous study demonstrated that the factors affecting the rate of colectomy at 1 year and the overall colectomy rate were i) CNI non-responsiveness, ii) >10,000 mg prednisolone used prior to the initiation of CNI treatment and iii) positivity for C7-horseradish peroxidase (HRP) (20). Based on these findings, the present study aimed to determine the factors that influence colectomy within 60 days of beginning treatment with CNIs using the Onodera-prognostic nutritional index (O-PNI).…”

Tacrolimus for remission induction in ulcerative colitis: Mayo endoscopic subscore 0 and 1 predict long-term prognosis

“…Bamba et al reported that factors affecting the rate of colectomy after tacrolimus or CsA induction therapy were: (i) CNI non-responsiveness; (ii) more than 10,000 mg of prednisolone used prior to the initiation of CNI treatment; and (iii) positive for C7-HRP [17]. Recently, Miyoshi et al assessed the endoscopic improvement and its impact on the medium and long-term prognosis after tacrolimus therapy.…”