Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. METHODS: In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. CONCLUSIONS: The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.     

Once-daily, high-concentration MMX mesalamine in active ulcerative colitis

BACKGROUND & AIMS: SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included. METHODS: Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline). RESULTS: A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated. CONCLUSIONS: Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.     

Efficacy of a daily application of mesalazine (Pentasa) suppository with progressive release, in the treatment of ulcerative proctitis. A double-blind versus placebo randomized trial]

Therapeutic efficacy of mesalazine controlled-release suppository 1 g once daily was compared with that of a placebo during 2 weeks in 50 patients (26 in the mesalazine group, 24 in the placebo group) with ulcerative proctitis, in a double-blind randomized trial. Endoscopic and clinical remission was seen in 69 and 65% of mesalazine-treated patients and in 33 and 25% of placebo-treated patients respectively (P < or = 0.01). No side effects were seen. It is concluded that a once-a-day administration of 1 g mesalazine controlled-release suppository is effective for topical treatment of patients with ulcerative proctitis.     

Combined Ciprofloxacin and Tinidazole Therapy in the Treatment of Chronic Refractory Pouchitis

Purpose Management of chronic refractory pouchitis, a common cause for pouch failure with pouch resection or diversion, is often challenging. The aim of this study was to assess the efficacy and safety of a combination therapy of ciprofloxacin and tinidazole in patients with chronic refractory pouchitis compared with mesalamine therapy. Methods Sixteen consecutive ulcerative colitis patients with chronic refractory pouchitis (disease>4 weeks and failure to respond to>4 weeks of single-antibiotic therapy) were treated with a four-week course of ciprofloxacin 1 g/day and tinidazole 15 mg/kg/day. A historic cohort of ten consecutive patients with chronic refractory pouchitis treated with oral (4 g/day), enema (8 g/day), or suppository (1 g/day) mesalamine served as controls. The Pouchitis Disease Activity Index, clinical remission, clinical response, the Cleveland Global Quality of Life, the Irritable Bowel Syndrome-Quality of Life, and the Short Inflammatory Bowel Disease Questionnaires scores were calculated before and after therapy and compared between the two treatment groups. Results Patients taking ciprofloxacin and tinidazole had a significant reduction in the total Pouchitis Disease Activity Index scores and subscores and a significant improvement in quality-of-life scores (P < 0.002). For patients in the mesalamine group, there was a significant reduction in the total Pouchitis Disease Activity Index scores only. Patients in the antibiotic group had a greater reduction in the total Pouchitis Disease Activity Index scores and a greater improvement in the quality-of-life scores than those in the mesalamine group (P ≤ 0.03). The rate of clinical remission and clinical response for the antibiotic group was 87.5 percent and 87.5 percent, respectively, and for the mesalamine group it was 50 percent and 50 percent, respectively (P = 0.069). Two patients in the antibiotic group (peripheral neuropathy and dysgeusia) developed adverse effects. Conclusions Combination therapy with ciprofloxacin and tinidazole was generally well tolerated and was effective in treating patients with chronic refractory pouchitis. Supported by National Institutes of Health grant NIH R03 DK 067275 and an American College of Gastroenterology Clinical Research Award (to B. S.).     

Comparison of oral with rectal mesalazine in the treatment of ulcerative proctitis

PURPOSE: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis. PATIENTS AND METHODS: A four-week, randomized, single-blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n=29) compared with 400 mg of mesalazine suppositories administered three times per day (n=29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports. RESULTS: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P<0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P<0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups. CONCLUSIONS: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.Presented at the meeting of Digestive Disease Week, San Francisco, California, May 19 to 22, 1996.     

Rebampide enema therapy as a treatment for patients with chronic radiation proctitis: initial treatment or when other methods of conservative management have failed

Introduction Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. There have been no formal trials of treatment for radiation proctitis and a variety of methods are currently used. We assessed the efficacy of rebamipide enema to control symptoms and proctoscopic findings from radiation proctitis. Materials and methods Fifteen patients with radiation proctitis were enrolled. Enemas containing 150 mg rebamipide per dosing were administered after morning bowel movement, and always prior to bedtime, twice daily for 4 weeks. The efficacy of treatment was assessed from clinical symptoms (Subjective Objective Management Analysis Scale for Rectal Toxicity) and endoscopic findings. Results The mean bleeding score improved from 2.67 to 0.53 (P < 0.01). The mean symptom scores improved in those patients who had pain (0.40 to 0.13), tenesmus (0.40 to 0.20), and stool frequency (0.27 to 0.13). The mean improvement in telangiectasia scores (2.13 to 0.80, P < 0.01), bleeding point scores (1.80 to 0.27, P < 0.01), and friable mucosa scores (1.33 to 0.20, P < 0.01) were all statistically significant. No side effects were noted in any patients. Conclusion Rebamipide enema therapy for radiation proctitis is a safe and effective treatment of radiation proctitis. We suggest the value of rebamipide enema in the treatment of radiation proctitis when other conservative management or first treatment has failed.     

Quality-of-life results of double-blind,placebo-controlled trial of mesalamine in patients with Crohn's disease

Seven quality-of-life parameters were assessed in a trial of mesalamine in Crohn's disease. The results with regard to efficacy and safety have been previously published. A total of 310 patients were enrolled in this double-blind, parallel trial and randomized to receive placebo, or 1, 2, or 4 g/day of mesalamine in controlled-release capsules for 16 weeks. Results revealed that mesalamine at the dose of 4 g/day resulted in significant (P<0.03) improvements from baseline in all quality-of-life parameters. A significant (P<0.02) linear trend between increasing doses of mesalamine and increasing response was also noted. The 1- and 2-g/day doses of mesalamine also resulted in an improvement in quality of life, however, with the exception of 2 g/day of mesalamine on the hobby and recreational activities parameter, these changes were not significantly different from placebo.Grant support for this trial was provided by Marion Merrell Dow Inc.     

Long-term maintenance treatment in ulcerative colitis: a 10-year follow-up

BACKGROUND: With the extensive use of mesalamine, the natural history of ulcerative colitis is probably changed. AIM: To evaluate the relapse rate and the duration of remission in patients with ulcerative colitis on maintenance treatment with mesalamine. PATIENTS AND METHODS: Enrolled in the study were 95 patients divided into 4 groups according to macroscopic location of the disease and treated with the same therapy starting from the date of enrolment. Patients in all 4 groups were followed-up until relapse occurred. The disease activity was evaluated by the Clinical Activity Index and Endoscopic Index. Patients suitable for recruitment showed a Clinical Activity Index and Endoscopic Index lower than 6 and 4, respectively. The patients with ulcerative pancolitis or left-sided colitis were treated with 1.6 g/day while the cases with proctosigmoiditis or proctitis were treated with 5-acetylsalicylic acid enemas 4 g/day Each patient was evaluated with clinical and endoscopic assessment at a 6-month interval. Relapse was defined as an increase in Clinical Activity Index and Endoscopic Index, of more than 6 and 4, respectively. RESULTS: Five patients dropped-out. All enrolled patients showed a clinical and/or endoscopic relapse within 10 years, the majority 2 or 3 years after diagnosis: pancolitis and left-sided colitis within 2-3 years and patients with distal colitis within 9-10 years. CONCLUSIONS: A relapse was observed in most cases within 3 years, and in all recruited patients within a space of ten years. The extent of the disease in the colon is an important prognostic factor, as patients with distal colitis showed a lesser tendency to relapse.     

Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study

Background—Daily administration of rectalformulations of mesalazine is effective in preventing relapse ofulcerative proctitis. Maintenance of remission with lower doses wouldbe an advantage.
Aim—The efficacy of mesalazine suppositories(Pentasa) 1 g three times a week v placebo to maintainremission in patients with cryptogenetic proctitis was studied.
Methods—Ninety five patients with cryptogeneticproctitis were randomised within two weeks of remission to receive forone year or until relapse three suppositories per week of eitherPentasa (n=48) or placebo (n=47). In the case of a relapse, thepatients received one suppository/day.
Results—It was found that 25 of 48 subjectsv 18 of 47 remained in remission in the mesalazine andplacebo groups respectively. The relapse rate was lower in themesalazine group for the following time intervals: 0-90 days (19%v 38%, p=0.035), 0-180 days (29% v 54%,p=0.017), 0-270 days (38% v 60%, p=0.031), and 0-365days (48% v 62%, p=0.18). Treatment of relapse with onesuppository/day induced remission in 11 of 18 and 2 of 26 patients inthe mesalazine and placebo groups respectively (p=0.001). Overall, 61%v 28% patients remained in the protocol and were inremission at one year (p=0.001). Tolerance was good.
Conclusion—Mesalazine suppositories 1 g threetimes a week are effective for preventing relapses of cryptogeneticproctitis. Increasing the dose to 1 g/day is effective in a highproportion of subjects who relapsed.

     

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease

PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohn's disease, with particular attention to the possible correlation with clinical features. METHODS: Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohn's disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9 percent), and 2 of 252 healthy subjects (<1 percent;P<0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43vs. 27 percent;P<0.002), and patients with Crohn's disease with colitis (27vs. 2.5 percent;P<0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18vs. 34 percent;P<0.0025). CONCLUSIONS: In this study we confirm the relative specific of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohn's disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.Presented in part at the Digestive Disease Week Meeting, San Francisco, California, May 19 to 22, 1996.     

Double-Blind Pilot Study of Mesalamine vs. Placebo for Treatment of Chronic Diarrhea and Nonspecific Colitis in Immunocompetent HIV Patients

Chronic diarrhea and colitis are common in patients positive for human immunodeficiency virus (HIV) under highly active antiretroviral treatment (HAART). This prospective double-blind study explores the effect of mesalamine vs. placebo in HIV-positive patients. Thirteen HIV-infected patients with noninfectious chronic diarrhea and > 250 CD4+ cells/mm³ were randomized to mesalamine (2.4 g/day; n = 9) or placebo (n = 4) for 6 weeks. Colonoscopy was performed at baseline and week 6, and biopsies were obtained to calculate the Biopsy Activity Index (BAI). Diarrhea was assessed at baseline and end of treatment using the Disease Activity Index (DAI). Patients and clinicians completed Patient Global Improvement index (PGI) and Clinical Global Improvement index (CGI) at weeks 2 and 6. Comparisons at week 6 were statistically significant between mesalamine and placebo groups for BAI (P = 0.03), DAI (P = 0.007), PGI (P = 0.008), and CGI (P = 0.008). Furthermore, major improvements were documented in the mesalamine group at week 6 compared to baseline for all variables, whereas the placebo group did not have any. Mesalamine was effective for treatment of chronic diarrhea and moderate nonspecific colitis in HIV patients.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis

PURPOSE: The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis. METHODS: Thirt-yeight patients with distal ulcerative colitis (n=17) or ulcerative proctitis (n=21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n=19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n=19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category. RESULTS: At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.280,P <0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P <0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts. CONCLUSION: These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.Read at the meeting of the First United European Gastroenterology Week, Athens, Greece, September 25 to 30, 1992.     

A double blind,randomized, placebo controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis

Objective: The efficacy of erythromycin in treatment of knee effusion due to osteoarthritis was evaluated. Method: We assessed efficacy and safety of erythromycin during 16 weeks in patients enrolled in a randomized double‐blind study. One hundred and eight patients with knee effusion due to osteoarthritis (OA) received 12‐week courses of erythromycin or placebo allocated randomly, and were followed for 4 months. Acetaminophen 650 mg/day was used in both groups, while they received no other anti‐inflammatory drugs (such as corticosteroid or nonsteroidal anti‐inflammatory drugs) during the course of the study. Our patients were divided in two groups, erythromycin in doses of 200 mg four times per day was given to the first group (51 patients) over the first 3 months of the study and in the second group we used placebo with the same dosage and schedule (53 patients). Outcomes improvement for the erythromycin‐treated group was assessed by a significantly higher mean score from baseline to the end of the trial, compared with placebo group. Patients were examined monthly during the treatment period. Measurement values included recording of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire subscales (pain, stiffness and function), range of motion and knee circumference. Results: Erythromycin produced a higher response rate than placebo in treatment of knee effusion due to OA. Significant reduction in knee circumference (P < 0.0005) and pain (P < 0.001) with functional improvement (P < 0.0005) were seen. At the first month after treatment, 11.8% (6 patients) in erythromycin and 9.4% (5 patients) in placebo groups had 50% pain reduction, which was not significant (P = 0.75). At the fourth month, 50% reduction of pain was seen in 45.1% (23 patients) of the erythromycin and 11.3% (6 patients) of the placebo group. This was statistically significant (P < 0.0005). Erythromycin treatment was well tolerated and mild adverse events caused no discontinuation during the study. Conclusion: This is a placebo‐controlled study of macrolid efficacy on knee effusion due to OA in a short period. Results of this research showed the better efficacy of erythromycin in controlling effusion and pain with functional improvement in patients with knee effusion due to OA.     

The usefulness of mesalazine suppositories for the treatment of lymphoid follicular proctitis]

BACKGROUND/AIMS: Lymphoid follicular proctitis (LFP) is an uncommon inflammatory condition confined to the rectum. Patients with LFP constitute a special group with clinical, endoscopic, and histological features unrelated to other types of inflammatory bowel diseases, and have been reported to be refractory to local steroid and/or oral sulfasalazine therapy. The aim of this study was to clarify whether mesalazine suppositories have a therapeutic effect in LFP. METHODS: The histologic slides of 8 cases indexed in our pathology files as "lymphoid follicular proctitis of the rectal mucosa" from January 2001 to November 2003 were reviewed retrospectively. RESULTS: The most common symptom in the patients with LFP was rectal bleeding. The endoscopic mucosal changes were discontinuous, sparing whole circumferential involvement, and were strictly confined to the rectum. Average period of medication was 12 months. All the symptomatic patients with LFP responded to mesalazine suppository therapy. In addition, these patients did not progress to other disease including ulcerative proctitis or lymphoma. CONCLUSIONS: Mesalazine suppository treatment is a useful therapeutic option for symptomatic patients with LFP.     

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.     

5-Aminosalicylic Acid Suppositories in the Maintenance of Remission in Idiopathic Proctitis or Proctosigmoiditis: A Double-Blind Placebo-Controlled Clinical Trial

Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.     

A Meta-Analysis of the Efficacy of Sulfasalazine in Comparison with 5-Aminosalicylates in the Induction of Improvement and Maintenance of Remission in Patients with Ulcerative Colitis

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.     

A Multicenter,Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

Background  

Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP.     

Lack of effectiveness of the platelet-activating factor antagonist SR27417A in patients with active ulcerative colitis: A randomized controlled trial

Background & Aims: Platelet-activating factor (PAF) is increased during relapse of ulcerative colitis. In animal models of experimental colitis, specific inhibition of PAF has reduced inflammation. The aim of this study was to evaluate the efficacy and safety of the PAF antagonist SR27417A in moderately active UC. Methods: A double-blind multicenter trial was conducted during a 28-day period in hospital outpatients with an exacerbation of ulcerative colitis. Patients were randomized to receive 10 mg/day SR27417A or placebo, and both groups were also given 2.4 g mesalazine. Patient classification at the end of the treatment period was based on sigmoidoscopy and clinical scores. Results: One hundred fifty-one subjects entered the study (75 placebo and 76 SR27417A). The remission rate between placebo- and SR27417A-treated patients at 28 days was not significantly different (29.0% and 35.6% respectively; P = 0.44). Similarly, 49.2% treated with SR27417A had a definite or possible improvement of their symptom score compared with 48.3% of those treated with placebo (P = 0.43). Four subjects in the placebo group and 5 subjects in the SR27417A group discontinued the drug treatment because of adverse events. No significant adverse events were thought to be caused by SR27417A. Conclusions: Although the specific PAF antagonist SR27417A is safe in humans, there is no evidence of efficacy in the treatment of acute ulcerative colitis.GASTROENTEROLOGY 1998;115:1340-1345     

Safety and Efficacy of New Glyceryl Trinitrate Suppository Formula: First Double Blind Placebo-Controlled Clinical Trial

Purpose  This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure. Methods  Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis. Results  Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05).The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05). Conclusions  Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure. Supported by Isfahan University of Medical Sciences and Poursina Hakim Research Institute. Read at the Iranian Congress of Gastroenterology and Hepatology (ICGH 2006), Tehran, Iran.