Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new asacol research articles will be listed here shortly after becoming available to us.
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Medical research on asacol
Colorectal Dis. 2008 Oct; 10(8): 814-7
Bresci G, Parisi G, Capria A
AIMS: To describe the long-term prognosis of ulcerative colitis (UC) and to establish whether a correlation exists between the different anatomic locations of the disease and the risk of relapse in a homogeneous cohort of patients with UC in clinical remission, all treated with fixed doses of oral mesalamine from the date of enrollment to the appearance of the first relapse. METHOD: We distinguished the patients with pancolitis and left-sided colitis from those with distal colitis. The follow-up lasted up to 5 and 6 years for the patients with pancolitis and left-sided colitis, respectively, and up to 9 years for the patients with distal colitis. RESULTS: One hundred and fifty patients satisfied the enrollment criteria. We registered 19 drop-outs. All the patients had relapsed within 9 years. In most cases relapses arose within 2-3 years. The patients with pancolitis had a shorter time to relapse (100% relapsed after 5 years) than the patients with left-sided colitis (100% after 6 years) or distal colitis (100% after 9 years). None of the enrolled patients developed a cancer. Extraintestinal complications were observed in 9% of cases and surgery was needed in five patients only. CONCLUSION: The first 2-3 years after the enrollment of patients with UC in remission was the period at higher risk of relapse. No relationship was found between the different anatomic locations of the disease and the risk of relapse, even if distal colitis showed a slightly better course.
Pharm Dev Technol. 2008 Sep 27; 1-10
Chuong MC, Christensen JM, Ayres JW
The goal was to use temporal gastrointestinal transit simulations and formulation to predict and provide sustained input of target-site directed oral drug delivery exclusively into the colon. Using mesalamine as the model drug for formulation coupled with stomach emptying rates (fed and unfed) plus intestinal transit times demonstrates concepts and provides a specific example for treatment in ulcerative colitis. Formulation involved extrusion and spheronization into beads which were then coated with aqueous Eudragit(R) S. Drug is released only at colonic pH and gastrointestinal transit predicts sustained drug input into the colon, especially when food effects are included.
Aliment Pharmacol Ther. 2008 Sep 19;
Irvine EJ, Yeh CH, Ramsey D, Stirling AL, R Higgins PD
Background: Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient-reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalamine. Aims: To examine the effect of mesalamine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalamine dose, and responder status on QoL parameters. Methods: Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from 2 double-blind, randomized, multicenter, active-controlled trials assessing 2.4 g/day and 4.8 g/day oral delayed-release mesalamine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks, and effects of baseline severity, mesalamine dose, and response to therapy were examined. Results: Mesalamine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P
The cost-utility of high dose oral mesalazine for moderately active ulcerative colitis.
Aliment Pharmacol Ther. 2008 Sep 20;
Buckland A, Bodger K
Background: Mesalazine is standard first line treatment for moderately active ulcerative colitis (UC). Recently, doubling the mesalazine dose (Asacol 4.8 g/day) was shown to improve efficacy with no increase in adverse events. The cost-effectiveness of this strategy is unknown. Aim: To assess the cost-utility of high dose (HD) mesalazine (Asacol 4.8 g/day) compared with standard dose (SD) mesalazine (Asacol 2.4 g/day) as first line treatment for moderately active UC. Methods: The costs and benefits associated with a treatment pathway beginning with HD or SD mesalazine were determined over 12 weeks using a decision tree analytical model. Results: A 12-week treatment pathway starting with HD mesalazine cost an average of pound2,382 per patient, compared with pound2,474 for SD mesalazine, and generated 0.0016 more quality adjusted life years (QALYs). HD mesalazine dominated SD mesalazine, being both more effective and less costly. HD mesalazine treatment resulted in fewer patients requiring surgery or hospitalisation for intensive pharmacological treatment. Probabilistic sensitivity analysis indicated a 72% chance that HD mesalazine was cost effective, based on a cost/QALY threshold of pound30,000. Conclusions: This study suggests that HD mesalazine represents a cost-effective alternative to SD mesalazine for moderately active UC, while potentially reducing the need for hospitalisation.
Pharm Dev Technol. 2008 Sep 18; 1-8
Patel MM, Shah TJ, Amin AF, Shah NN
The aim of present study was to develop a time- and pH-dependent system for delivering mesalamine to the colon. The system consists of the core tablet of mesalamine which is compression coated with hydroxypropyl methylcellulose (HPMC K4M) (time-dependent factor). This is then coated with pH-dependent polymer Eudragit(R) L100. The simplex lattice design was adopted to optimize the independent variables i.e. amount of HPMC (X1), dextrose (X2) and polyvinyl pyrollidone (PVP) (X3) and to study their effect on the dependent variables i.e. lag time and time for 50% drug dissolution (t50). The results of the linear interactive model and graphical representation revealed that as the amount of HPMC increases, the lag time and t50 value also increases and as the amount of dextrose and PVP were increased the lag time and t50 value decreases.
Design of a potential colonic drug delivery system of mesalamine.
Pharm Dev Technol. 2008; 13(5): 447-56
Gohel MC, Parikh RK, Nagori SA, Dabhi MR
The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.
Am J Gastroenterol. 2008 Sep 4;
Yen EF, Kane SV, Ladabaum U
OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA, mesalamine) is effective in inducing and maintaining remission in ulcerative colitis (UC). The relative benefits and costs of maintenance 5-ASA therapy are uncertain. Our aims were to evaluate this strategy's potential cost-effectiveness. METHODS: We constructed a Markov model to compare two strategies over 2 yr: (a) no maintenance 5-ASA, with 5-ASA 4.8 g/day given for flares, (b) maintenance 5-ASA 2.4 g/day, escalated and maintained at 4.8 g/day after the first flare. In both arms, the failure to induce remission led to other treatments, as needed: prednisone, parenteral corticosteroids, cyclosporine, 6-mercaptopurine, infliximab, and colectomy. RESULTS: Without maintenance 5-ASA, the mean flares per person were 1.92, and the mean cost per person was $3,402. With maintenance 5-ASA providing a relative risk of flare of 0.7 at 5-ASA cost of $198/month, flares per person decreased to 1.38 at a cost of $8,810/flare prevented. Maintenance 5-ASA increased discounted quality-adjusted life-years per person (QALYs per person) from 1.75 to 1.77 at a discounted cost of $224,000/QALY gained. The results were most sensitive to the flare risk reduction and cost of 5-ASA, the utilities of being in remission without or with 5-ASA, and the colectomy rates. At $15/month (the cost of sulfasalazine), maintenance 5-ASA cost $640/flare prevented and $16,300/QALY gained. CONCLUSION: Maintenance 5-ASA therapy decreases UC flares, but its cost may be substantial, depending on society's willingness to pay. If sulfasalazine can be tolerated and yields comparable benefits, sulfasalazine maintenance therapy is likely to be cost-effective. The cost per QALY gained by 5-ASA maintenance is highly dependent on the quality of life while taking versus not taking maintenance 5-ASA, highlighting the importance of patients' preferences.
Dig Dis Sci. 2008 Sep 4;
Nikfar S, Rahimi R, Rezaie A, Abdollahi M
Background Historically, sulfasalazine (SSZ) and 5-aminosalicylates (5-ASAs) have been a mainstay of mild-to-moderate ulcerative colitis (UC) remission induction and maintenance therapy. Considering the pivotal role of intestinal microbial flora in pathophysiology of UC and antimicrobial activity of sulfapyridine, we hypothesized that SSZ might be more effective than 5-ASAs in the management of UC. Aim To compare the efficacy and tolerability of SSZ with each of the 5-ASAs (mesalamine, olsalazine, and balsalazide) by a meta-analysis technique. Methods Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies compared efficacy and/or tolerability of SSZ with 5-ASAs in the management of UC. The search terms were: "sulfasalazine" or "sulfasalazine" and "5-aminosalicylic acid," "mesalazine," "mesalamine," "olsalazine" or "balsalazide" and "ulcerative colitis." Data were collected from 1966 to April 2008. There was no language restriction. "Overall improvement," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. Results Twenty randomized placebo controlled trials met our criteria and were included in the meta-analysis. Comparison of SSZ with mesalamine yielded a nonsignificant relative risk (RR) of 1.04 (95% confidence interval of 0.89-1.21, P = 0.63) for overall improvement, a nonsignificant RR of 0.98 (95% CI 0.78-1.23, P = 0.85) for relapse, a nonsignificant RR of 0.76 (95% CI 0.54-1.07, P = 0.11) for any adverse events, and a nonsignificant RR of 0.78 (95% CI 0.46-1.3, P = 0.33) for withdrawals due to adverse events. Comparison of SSZ with olsalazine yielded a nonsignificant RR of 1.14 (95% CI 0.91-1.43, P = 0.25) for overall improvement, a nonsignificant RR of 0.93 (95% CI 0.77-1.12, P = 0.42) for relapse, a nonsignificant RR of 1.21 (95% CI 0.9-1.61, P = 0.20) for any adverse events, and a nonsignificant RR of 1.53 (95% CI 0.93-2.52, P = 0.09) for withdrawals due to adverse events. Comparison of SSZ with balsalazide yielded a nonsignificant RR of 1.3 (95% CI 0.93-1.81, P = 0.12) for overall improvement, and a significant RR of 0.17 (95% CI 0.06-0.49, P = 0.001) for withdrawals because of adverse events. Conclusion SSZ does not differ from mesalamine or olsalazine in terms of efficacy and tolerability in UC. Withdrawal from study due to adverse events was significantly lower for balsalazide compared with SSZ. Convincing conclusions on the comparison of effectiveness and safety of balsalazide and SSZ in UC remains to be elucidated by further clinical trials. Considering the lower cost of treatment with SSZ and the equal rate of adverse events with other 5-ASAa, it is not surprising to suggest SSZ as a first-choice treatment for UC and reserve 5-ASAs for when SSZ intolerability occurs.
Am J Gastroenterol. 2008 Aug 21;
Bossa F, Latiano A, Rossi L, Magnani M, Palmieri O, Dallapiccola B, Serafini S, Damonte G, De Santo E, Andriulli A, Annese V
BACKGROUND AND AIM: Nearly 25% of patients with ulcerative colitis (UC) requiring steroids therapy become steroid-dependent after 1 yr, and virtually all develop steroid-related adverse events. We planned a controlled study to investigate the efficacy and safety of dexamethasone 21-P (Dex 21-P) encapsulated into erythrocytes (DEE). MATERIALS AND METHODS: Forty patients with mild-to-moderate UC, refractory to mesalamine, were randomly assigned to one of the following three treatments: two DEE infusions 14 days apart (group A, N = 20), oral prednisolone (0.5 mg/kg for 14 days followed by a 6 mg/weekly tapering (group B, N = 10), and sham infusions (group C, N = 10). The clinical, biochemical, and endoscopic parameters were monitored at inclusion and after 8 wk. RESULTS: In group A, a mean dose of 9.9 +/- 4.1 mg Dex 21-P was loaded into autologous erythrocytes at each infusion. At 8 wk, 15 patients in group A (75%), 8 in group B (80%), and 1 in group C (10%, P < 0.001 vs A and B) were in clinical and endoscopic remission. When compared with the baseline values, C-reactive protein (CRP) dropped in groups A (1.6 mg/dL vs 0.4 mg/dL, P= 0.006) and B (1.0 vs 0.5, P= 0.02), but not in group C. No steroid-related adverse events were apparent in the patient treated with DEE, compared with 8 out of 10 patients on oral steroids (P
Dig Dis Sci. 2008 Aug 21;
Ancha HR, Kurella RR, McKimmey CC, Lightfoot S, Harty RF
The aim of the present studies was to examine mechanisms by which the rectally administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA) affects inducers of inflammation to promote mucosal healing and reduce tissue inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA was superior to individual agents in reducing histological measures of colitis. NAC alone and in combination with 5-ASA suppressed COX2 gene expression and prostaglandin E(2) (PGE(2)) levels to control values. Furthermore, NAC plus 5-ASA reduced nitrate generation, an expression of inducible nitric oxide synthase (iNOS) activity, to basal levels and these results were significantly lower than those observed with either NAC or 5-ASA alone. In conclusion, these results indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering the actions of PGE(2) and the deleterious effects of oxidative and nitrosative stress induced by TNBS colitis.