Maintaining Remission in Patients With Ulcerative Colitis
Maintaining Remission in Patients With Ulcerative Colitis
Of 562 patients in the combined ITT population from the two studies, 487 subjects were receiving 5-ASA maintenance therapy at enrolment (i.e. 5-ASA subgroup); n = 322 in the MG group and n = 165 in the placebo group (Figure 1). 5-ASA formulations used prior to randomisation are presented in Figure 2.
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Figure 1.
Patient disposition for subpopulation of patients in the ITT population from both studies, who were using other 5-ASA formulations to maintain remission before switching to either MG 1.5 g or placebo. The category 'UC relapse' above includes patients who withdrew with a reason of lack of efficacy and/or due to a UC-related adverse event, as mandated per protocol, to receive standard of care.
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Figure 2.
5-ASA formulations used to maintain UC remission before patients switched to either MG 1.5 g or placebo upon randomisation into study. Some subjects used multiple formulations; therefore the total number of 5-ASA formulations (522) is greater than the number of subjects (487).
Demographic and baseline disease characteristics were similar between treatment groups (Table 1). The mean duration of current remission was 17 weeks in both groups, and the time since the most recent UC flare was 25 and 26 weeks in the MG and placebo groups respectively. The respective mean baseline total SDAI scores were 0.8 and 1.0.
The mean (± standard deviation) overall compliance for the MG and placebo subpopulations for the duration of the treatment period were 97.2% (±7.5%) and 96.9% (±6.1%) respectively.
A statistically significant higher percentage of patients who received MG remained relapse-free compared with placebo in the 5-ASA subgroup. Overall, 78.3% of patients who received MG remained relapse-free after 6 months compared with 58.8% of patients who received placebo. In addition to the positive results for the combined 5-ASA subgroup analyses presented herein, statistically significant results for the a priori analysis of the primary endpoint were demonstrated independently for both trials, MPUC3003, study MPUC3004 and the analysis for pooled data from both trials (Table 2).
Statistically significant differences MG over placebo were observed for most secondary efficacy endpoints including the proportions favouring of patients at each level of change from baseline in SDAI scores for rectal bleeding (P = 0.004), physicians' rating of disease activity (P = 0.004) and stool frequency (P = 0.002) and the mean change from baseline in the SDAI total score (P < 0.001) (Table 3), indicating that significantly fewer patients in the MG group experienced rectal bleeding or other symptoms of UC during the 6-month treatment period. The change from baseline in the mucosal appearance component of the SDAI score showed a trend favouring MG over placebo; however, a statistically significant difference was not observed over the 6 months treatment period.
The probability of patients remaining relapse-free over 6 months was significantly improved in the MG-treated group vs placebo (Table 3; P < 0.001). In addition, these data (Figure 3) demonstrate that the patients who switched to MG had a greater probability of remaining relapse-free compared with patients who received placebo (P < 0.001).
(Enlarge Image)
Figure 3.
Kaplan–Meier estimates of time to relapse during the treatment period in ITT patients who switched from other 5-ASA formulations to either MG 1.5 g or placebo.
Adverse events reported in at least 3% of patients and reported more frequently with MG than placebo are presented in Table 4, and are similar to what was reported earlier and are consistent with the more common adverse reactions reported in clinical trials with mesalazine. Serious AEs were reported in six patients: three patients who received MG and three in the placebo group. The incidence of AEs leading to premature withdrawal from the study was lower in MG group (10.9%) compared with placebo (19.8%), largely due to a lower incidence of UC flares leading to premature withdrawal in patients receiving MG (6.9%) compared with placebo (16.0%). AEs affecting the renal or hepatic systems were rare.
Results
Patients
Of 562 patients in the combined ITT population from the two studies, 487 subjects were receiving 5-ASA maintenance therapy at enrolment (i.e. 5-ASA subgroup); n = 322 in the MG group and n = 165 in the placebo group (Figure 1). 5-ASA formulations used prior to randomisation are presented in Figure 2.
(Enlarge Image)
Figure 1.
Patient disposition for subpopulation of patients in the ITT population from both studies, who were using other 5-ASA formulations to maintain remission before switching to either MG 1.5 g or placebo. The category 'UC relapse' above includes patients who withdrew with a reason of lack of efficacy and/or due to a UC-related adverse event, as mandated per protocol, to receive standard of care.
(Enlarge Image)
Figure 2.
5-ASA formulations used to maintain UC remission before patients switched to either MG 1.5 g or placebo upon randomisation into study. Some subjects used multiple formulations; therefore the total number of 5-ASA formulations (522) is greater than the number of subjects (487).
Demographic and baseline disease characteristics were similar between treatment groups (Table 1). The mean duration of current remission was 17 weeks in both groups, and the time since the most recent UC flare was 25 and 26 weeks in the MG and placebo groups respectively. The respective mean baseline total SDAI scores were 0.8 and 1.0.
The mean (± standard deviation) overall compliance for the MG and placebo subpopulations for the duration of the treatment period were 97.2% (±7.5%) and 96.9% (±6.1%) respectively.
Primary Efficacy Endpoint: Proportion of Relapse-free Patients in the 5-ASA Subgroup
A statistically significant higher percentage of patients who received MG remained relapse-free compared with placebo in the 5-ASA subgroup. Overall, 78.3% of patients who received MG remained relapse-free after 6 months compared with 58.8% of patients who received placebo. In addition to the positive results for the combined 5-ASA subgroup analyses presented herein, statistically significant results for the a priori analysis of the primary endpoint were demonstrated independently for both trials, MPUC3003, study MPUC3004 and the analysis for pooled data from both trials (Table 2).
Secondary Efficacy Endpoints in the 5-ASA Subgroup
Statistically significant differences MG over placebo were observed for most secondary efficacy endpoints including the proportions favouring of patients at each level of change from baseline in SDAI scores for rectal bleeding (P = 0.004), physicians' rating of disease activity (P = 0.004) and stool frequency (P = 0.002) and the mean change from baseline in the SDAI total score (P < 0.001) (Table 3), indicating that significantly fewer patients in the MG group experienced rectal bleeding or other symptoms of UC during the 6-month treatment period. The change from baseline in the mucosal appearance component of the SDAI score showed a trend favouring MG over placebo; however, a statistically significant difference was not observed over the 6 months treatment period.
The probability of patients remaining relapse-free over 6 months was significantly improved in the MG-treated group vs placebo (Table 3; P < 0.001). In addition, these data (Figure 3) demonstrate that the patients who switched to MG had a greater probability of remaining relapse-free compared with patients who received placebo (P < 0.001).
(Enlarge Image)
Figure 3.
Kaplan–Meier estimates of time to relapse during the treatment period in ITT patients who switched from other 5-ASA formulations to either MG 1.5 g or placebo.
Safety in the 5-ASA Subgroup
Adverse events reported in at least 3% of patients and reported more frequently with MG than placebo are presented in Table 4, and are similar to what was reported earlier and are consistent with the more common adverse reactions reported in clinical trials with mesalazine. Serious AEs were reported in six patients: three patients who received MG and three in the placebo group. The incidence of AEs leading to premature withdrawal from the study was lower in MG group (10.9%) compared with placebo (19.8%), largely due to a lower incidence of UC flares leading to premature withdrawal in patients receiving MG (6.9%) compared with placebo (16.0%). AEs affecting the renal or hepatic systems were rare.