Real life results in using 5-ASA for maintaining mild to moderate UC patients in Japan, a multi-center study, OPTIMUM Study

Abstract

Background: Efficacy of maintenance therapy in ulcerative colitis (UC) in the remission stage has been reported to depend on release profile or dosing regimen of oral 5-aminosalicylic acid (5-ASA) products used. Aim of this study is to investigate real life results in using oral 5-ASA products for maintaining mild to moderate UC patients in Japan.

Methods: Adult UC outpatients treated with oral 5-ASA products were enrolled from 379 sites in Japan between July 2012 and July 2013, and followed for 52 weeks. Remission maintenance rate was evaluated by products and dosages. Factors affecting recurrence were also examined.

Results: A total of 5695 UC patients were registered. Among the 4677 patients in whom remission maintenance was observed, remission maintenance rate at week 52 was 80.2%. As for disease duration and dosage, Pentasa® 4000 mg/day in 2 divided doses was administered to 480 (21.0%) patients in remission and 341 (46.6%) patients in active stage, and Asacol® 3600 mg/day in 3 divided doses was administered to 696 (46.4%) patients in remission and 473 (67.3%) patients in active stage. The remission maintenance rate at week 52 by dosage and frequency did not significantly differ between Pentasa® Tablets at 4000 mg/day in 2 divided doses (76.5%) and Asacol® Tablets at 3600 mg/day in 3 divided doses (76.1%, P = 0.7868). Factors affecting the risk of relapse in UC were identified. Significantly persistent remission maintenance was noted in patients in whom duration of remission maintenance until enrollment was 12 to <24 months or ≥24 months relative to the reference category of <3 months (12 to <24 months: HR 0.600 [0.486-0.740], p < 0.0001]; ≥24 months: HR 0.352 [0.289-0.431], p < 0.0001).

Conclusions: Efficacy of real life results in using oral 5-ASA products for maintaining mild to moderate UC patients was favorable. Maintaining remission for 12 months or longer after induction therapy was shown to reduce recurrence risk thereafter.

Trial registration: UMIN 000008563 (the date of registration: July 30, 2012), ClinicalTrials.gov NCT01654783 (the date of registration: July 30, 2012).

Keywords: Observational study; Oral 5-ASA products; Remission maintenance rate; Ulcerative colitis.

Fig. 1

Patient Disposition

Fig. 2

Number of Patients by Disease Stage at Enrollment and by Drug. a Daily dose of Pentasa® b Daily dose of Asacol® c Daily dose of Salazopyrin®

Fig. 3

Cumulative remission maintenance rate

Fig. 4

Remission maintenance rates. a Comparison by drug. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by the extent of lesion, classification by clinical course, smoking habit, concomitant use of drugs for UC other than probiotics/cytapheresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment). b Comparison between Pentasa® Tablets at 4000 mg/day in 2 divided doses and Asacol® Tablets at 3600 mg/day in 3 divided doses. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by the extent of lesion, classification by clinical course, smoking habit, concomitant use of drugs for UC other than probiotics/cytapheresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment). c Comparison between Pentasa® Tablets at 2000 mg/day in 1 dose and Asacol® Tablets 2400 mg/day in 3 divided doses. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by the extent of lesion, classification by clinical course, smoking habit, concomitant use of drugs for UC other than probiotics/cytapheresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment). d Comparison by the extent of lesion. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by clinical course, smoking habit, concomitant use of drugs for UC other than probiotics/cytapheresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment). e Comparison by clinical course. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by the extent of lesion, smoking habit, concomitant use of drugs for UC other than probiotics/cytapheresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment)

Fig. 5

Remission Maintenance Rate by the Presence or Absence of Dose Reduction after Remission has been Induced. Cochran-Mantel-Haenszel test. Adjustment factors: age (≤60 years, ≥61 years), classification by the extent of lesion, classification by clinical course, smoking habit, concomitant use of drugs for UC other than probiotics/cytaphresis therapy, duration of disease, duration of remission maintenance until enrollment (0 for patients in the active stage at enrollment)