Multimatrix Mesalazine Research Articles

Real-world experience with MMX mesalazine use in Mexican patients with ulcerative colitis at two tertiary care centers

Introduction and aimsThe 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers. Materials and methodsA retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction. ResultsThe frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented. ConclusionsThere were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in ashort follow-up period.

The impact of clinical symptoms and endoscopic and histologic disease activity on health-related quality of life in patients with ulcerative colitis following treatment with multimatrix mesalazine

PurposeStudies of patients with ulcerative colitis (UC) report that reduced clinical symptoms and endoscopic activity predict better health-related quality of life (HRQoL). However, no study has examined the joint and unique associations of clinical and endoscopic activity with HRQoL, nor of histologic inflammation and HRQoL. These post hoc analyses evaluated whether reduced clinical, endoscopic, and histologic disease activity were uniquely associated with improved HRQoL for adults with active mild-to-moderate UC receiving once-daily 4.8 g/day multimatrix mesalazine for 8 weeks.MethodsAssessments at baseline and week 8 (i.e., treatment completion) included clinical and endoscopic activity (modified UC-Disease Activity Index), histology (Geboes scoring), and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]; SF-12v2® Health Survey [SF-12v2]). Associations among each type of disease activity and HRQoL were examined by correlations and by mean changes in SIBDQ and SF-12v2 scores between disease activity subgroups (e.g., achievement of clinical remission; mucosal healing). Regression models estimated unique variance in HRQoL accounted by each type of disease activity.ResultsWithin the analysis sample (n = 717), patients with reduced clinical and endoscopic activity had significantly larger improvements in all HRQoL domains (p < 0.001), as did patients in both endoscopic and clinical remission compared to patients in endoscopic remission only (p < 0.05). Patients with histologic activity post-treatment scored significantly worse on all HRQoL domains than patients with no activity (p < 0.05). Correlations and regression models found that decreases in clinical and endoscopic activity were associated with improvements in HRQoL domain scores.ConclusionsClinical symptoms and mucosal health have separable, distinct impacts on UC patients’ HRQoL.

Differential effects of mesalazine formulations on thiopurine metabolism through thiopurine S-methyltransferase inhibition.

Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5-aminosalicylic acid (5-ASA). 5-ASA is known to inhibit thiopurine S-methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance. Plasma concentrations of 5-ASA, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time-dependent or pH-dependent mesalazine or MMX) as monotherapy. Patients already on both time-dependent or pH-dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) 0 and 8weeks after switching. Clinical relapse after switching was also monitored for 24weeks. Plasma 5-ASA and N-Ac-5-ASA levels were significantly higher in patients receiving time-dependent mesalazine (n=12) compared with pH-dependent mesalazine (n=12) and MMX (n=15), accompanied by greater TPMT inhibition. Prospective switching from time-dependent mesalazine to MMX decreased 6-TGN levels, increased those of 6-MMP, and increased 6-MMP/6-TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH-dependent mesalazine to MMX. Time-dependent mesalazine has higher plasma 5-ASA and N-Ac-5-ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time-dependent mesalazine to MMX may lead to an increase of 6-MMP/6-TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch.

Time to Symptom Resolution in Ulcerative Colitis With Multimatrix Mesalazine Treatment: A Pooled Analysis

Patients with ulcerative colitis [UC] require rapid and complete relief of symptoms, particularly stool frequency and rectal bleeding. The aim of this study was to determine time to symptom resolution in patients with UC during induction treatment with multimatrix mesalazine, and the proportion of patients remaining symptom-free and in endoscopic remission after 12 months of maintenance. A pooled analysis of 5 pivotal clinical trials, including >1300 patients, evaluating multimatrix mesalazine for treatment of mild-to-moderate active UC was conducted. Time to symptom resolution was defined as the period between first drug dosage date and first 3 consecutive days of induction therapy when the patient achieved a score of 0 [normal] on a modified UC Disease Activity Index for stool frequency and/or rectal bleeding. Median [95% confidence interval] time to resolution of stool frequency was 52 (45-not estimable [NE]) days for placebo versus 38 [34-41] days for multimatrix mesalazine [combined dose groups, 2.4 or 4.8 g/day]; time to resolution of rectal bleeding was 35 [20-NE] days for placebo versus 15 [14-17] days for multimatrix mesalazine [combined dose groups]. Among those who achieved resolution of both stool frequency and rectal bleeding during induction, 67.4% maintained symptom scores of 0 at Month 12. No relationship was observed between rapidity of symptom resolution during induction treatment and achievement of endoscopic remission at Month 12. Induction with multimatrix mesalazine provided rapid and prolonged symptom resolution in addition to endoscopic remission at Month 12.

Клинико-экономическая эффективность мультиматричного месалазина в терапии неспецифического язвенного колита в условиях здравоохранения Республики Казахстан

Aim: Clinical and economic evaluation of multi-matrix mesalazine 1200 mg compared with prolonged-release mesalazine at a dose of 500mg for the treatment of patients aged 18 years and older with the diagnosis of ulcerative colitis in the phase of exacerbation and remission. Material and methods: In accordance with the PICOS tool all published literature sources were identified in the electronic resources PubMed/Medline, DARE, Cochrane Central Register of Controlled Trials; the analysis included 5 studies with levels of evidence A and B. Calculations were performed in STATA and Microsoft Excel 10.0 Results and discussion: According to the results of clinical and economic analysis, the strategy of using multi-matrix mesalazine is dominant in comparison with prolonged-release mesalazine as a first-line therapy and contributes to the increment of efficiency and leads to the minimization of costs to achieve a QALY unit per patient. Patients receiving multi-matrix mesalazine have a longer duration of remission and less likelihood of re-exacerbations. Conclusion: The use of multi-matrix mesalazine in comparison with prolonged-release mesalazine is an economically feasible alternative in the conditions of health care of the Republic of Kazakhstan – more effective and less financially costly, leading to potential budget savings.

Comparison of efficacy of once daily multimatrix mesalazine 2.4 g/day and 4.8 g/day with other 5-aminosalicylic acid preparation in active ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day.MethodsIn this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score.ResultsThe mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety.ConclusionsThis study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Comparison of efficacies of once-daily dose multimatrix mesalazine and multiple-dose mesalazine for the maintenance of remission in ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission.MethodsIn this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding.ResultsThe proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety.ConclusionsA once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.

Comparison of efficacy of multimatrix mesalazine 4.8 g/day once-daily with other high-dose mesalazine in active ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine.MethodsIn this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period.ResultsThe change in the UC-DAI (mean±standard deviation) in the per-protocol set was −2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and −1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was −0.7 (two-sided 95% confidence interval, −1.3 to −0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups.ConclusionsMultimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.

PTU-091 Multimatrix mesalazine in paediatric ulcerative colitis: a pharmacokinetic and safety study

Introduction Data on mesalazine (5-aminosalicylic acid; 5-ASA) use in cases of paediatric ulcerative colitis (UC) are limited. In this phase 1, randomised, open-label, multicentre study ([NCT01130844][1]), pharmacokinetic (PK) and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) were examined in youth with UC diagnoses after once-daily (QD) multimatrix mesalazine administration. Method Upon enrolment, patients (pts; aged 5–17 y with diagnosis of UC ≥3 mo, stratified by body weight) were given 30, 60, or 100 mg/kg multimatrix mesalazine QD for 1 wk. The existing, approved, 1200 mg tablet was supplemented with newly developed, smaller-sized 300 and 600 mg multimatrix mesalazine tablets in order to achieve the appropriate study doses in children. Mesalazine was administered at home (Days 1–4) and at the clinic (Days 5–7); onsite, safety evaluations were performed, and blood and urine samples obtained for PK analyses. A validated LC/MS/MS assay was used to determine plasma and urine concentrations of 5-ASA and Ac-5-ASA. Key PK parameters assessed included maximum concentration (Cmax, ss), time of Cmax, ss (tmax), area under the curve for 1 dose interval (AUCss), renal clearance (CLR), and% dose absorbed. Results In total, 52 pts (21, 22, and 9 pts at 30, 60, and 100 mg/kg, respectively) were randomised and treated. Mean (standard deviation) age was 13.3 (3.1) y, and median (range) time since UC diagnosis was 1.8 (0.2–9.6) y. By Day 5, 5-ASA and Ac-5-ASA plasma concentrations reached steady state for all dose groups. On Day 7, for both 5-ASA and Ac-5-ASA, mean Cmax, ss and AUCssshowed dose proportional increases from 30 to 60 mg/kg cohorts. Mean% 5-ASA absorbed for 30, 60, and 100 mg/kg doses were 29.4%, 27.0%, and 22.1%, respectively. Mean CLR ranges were 5.0–6.5 L/h for 5-ASA and 10.0–16.2 L/h for Ac-5-ASA. Treatment-emergent adverse events (TEAEs) were reported by 19.2% of pts; no new safety signals were identified. Events were similar among age and dose groups, and no TEAEs led to premature discontinuation. Conclusion The PK profiles of 5-ASA and Ac-5-ASA in children and adolescents with UC receiving multimatrix mesalazine across all dose levels were similar to those from historical adult data with respect to absorption, clearance, and intersubject variability. Overall, multimatrix mesalazine was well tolerated with no new safety concerns identified. Disclosure of interest C. Cuffari Consultant for: Shire, Prometheus, Abbott Nutrition, D. Pierce Shareholder of: Shire, GlaxoSmithKline, Employee of: Former employee of Shire, B. Korczowski Grant/Research Support from: Shire, K. Fyderek Grant/ Research Support from: Shire, H. Van Heusen Shareholder of: Shire, Employee of: Shire, S. Hossack Employee of: Covance, which received funding from Shire, P. Martin Shareholder of: Shire, Employee of: Shire. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01130844&atom=%2Fgutjnl%2F64%2FSuppl_1%2FA101.1.atom

P607. Histologic activity after acute treatment with multimatrix mesalazine for ulcerative colitis may predict long-term remission status

P607. Histologic activity after acute treatment with multimatrix mesalazine for ulcerative colitis may predict long-term remission status

P538. Pooled safety analysis of long-term, once-daily multimatrix mesalazine use

P538. Pooled safety analysis of long-term, once-daily multimatrix mesalazine use