3b). Overall colectomy-free survival was 46.4% (Fig. 4a). Similarly, the addition
of AZA after CSA treatment significantly reduced the colectomy rate (Fig. 4b). Among CSA responders, AZA naïve patients (patients who did not receive AZA prior to CSA treatment) had a significantly lower probability of a colectomy than patients with prior AZA treatment (Fig. 4c). Among patients treated with a starting dose of 4 mg/kg per day of CSA, the first concentration of serum CSA was often over 600 ng/mL. A starting dose of 3 mg/kg per day significantly reduced initial serum CSA levels (463.0 ± 82.3 vs 611.0 ± 90.8, P < 0.0001). The rate of CSA effectiveness and adverse events was not significantly different between a starting dose of 3 mg/kg per day and 4 mg/kg/day (data not shown). There were no serious bacterial infections that occurred during CSA treatment. The administration of CSA was discontinued in four cases: two cases due to liver dysfunction, one due to renal dysfunction Omipalisib in vivo and one due IWR-1 manufacturer to a concomitant mental disorder. An antihypertensive drug was started in one case during
CSA treatment. A magnesium agent was administrated in four cases due to hypomagnesemia. This retrospective study describes the experience of CSA therapy and the efficacy of an immunomodulator (AZA) as a bridging therapy. In our results, the short-term efficacy rate of CSA was approximately 70%, which is similar to previous reports from Western countries. Short-term efficacy was affected by three factors: Endonuclease (i) more than 10 000 mg of PSL prior to CSA treatment; (ii) positivity for C7-HRP; and (iii) disease duration more than 4 years. High amounts of PSL and long disease duration might indicate the disease severity and refractoriness and these two factors might confound with each other. Although C7-HRP-positive patients were treated with concomitant gancyclovir treatment, CSA-related immunosuppression might stimulate cytomegalovirus activity,8
resulting in a decrease in the response rate. The administration of AZA after successful CSA treatments was the sole element that prolonged relapse-free survival at 1 year and colectomy-free survival. On the other hand, CSA responders with prior AZA treatment demonstrated poor responses and received colectomies. Our observations suggest a need for surgical intervention in patients with AZA administration prior to CSA treatment. Initially, we followed the regimen of Lichtiger et al. (starting dose of 4 mg/kg per day) at the beginning of the CSA treatment.5 However, 3 mg/kg per day was sufficient to keep serum CSA levels at 350–450 ng/mL. CSA is primarily eliminated through biotransformation by cytochrome P450 (CYP)3A in the intestinal wall and liver, excreted to bile juice. However, the clearance of CSA differs between Japanese and white populations. Japanese populations have lower CSA clearance compared to white.9 Thus, we recommend a starting dose of 3 mg/kg per day CSA.