Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects

BACKGROUND: Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects. AIM: To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis. METHODS: Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid. RESULTS: Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid. CONCLUSIONS: 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis

Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N=29) or oral sulfasalazine (N=31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.Presented in part at the International Meeting, Clinical Controversies in Inflammatory Bowel Disease, September 9 to 11, 1987, Bologna, Italy.     

Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis

The therapeutic efficacy of a slightly acidic, buffered suspension of 1000 mg 5-aminosalicylic acid (Pentasa^®) was compared with that of 25 mg prednisolone following daily rectal administration to outpatients with mild to moderate proctosigmoiditis. The study was carried out as a randomized, double-blind trial in seven gastroenterological departments. A total of 123 patients were included of whom 114 completed the study (53 5-aminosalicylic acid, 61 prednisolone). The patient population was representative for the disease as it ordinarily appears in medical outpatient clinics. After 14 days, patients in total remission discontinued the treatment, while the rest were treated for another two-week period. Improvement or remission was seen in 77% of the 5-aminosalicylic acid-treated patients and in 72% of the prednisolone-treated patients (P>0.05). More than half the patients requiring prolonged treatment benefited from it, which points to an advantage of extended therapy. Side effects were few and mild. It is concluded that the applied suspension of 5-aminosalicylic acid is at least as efficient as prednisolone for topical treatment of patients with slightly to moderately active proctosigmoiditis.The group includes: Vibeke Binder, MD, Stig Bondesen, MD, Olaf Bonnevie, MD, Knud Christian Christensen MD, Lisbeth Ambrosius Christensen, MD, Poul Danø, MD, Hans Draminsky Petersen, MD, Troels Havelund, MD, Eigill F. Hvidberg, MD, Oli Jacobsen, MD, Karin Ladefoged, MD, Karsten Lauritsen, MD, Laurits Stærk Laursen, MD, Jørgen Rask-Madsen, MD, Sten Nørby Rasmussen, MD, German Sanchez, MD, Poul Schlichting, MD, Ulrik Tage-Jensen, MD, Mogens Vilien, MD, Johann Wandall, MD.     

Mesalazine (5-aminosalicylic acid) induced chronic hepatitis

BACKGROUND: Treatment of ulcerative colitis or Crohn's disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported. CASE REPORT: A 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration. CONCLUSION: Contrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.     

Quantitative distribution of radiolabeled 5-Aminosalicylic acid enemas in patients with left-sided ulcerative colitis

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with^99mTc and to quantitate the distribution of [^99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [^99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P<0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P< 0.05) and at 2 hr (P< 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [^99mTc]5-ASA enemas reliably reach the area of inflammation.Supported by a grant from Reid-Rowell, Inc.     

Retrograde spread of 5-aminosalicylic acid enemas in patients with active ulcerative colitis

In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.     

5-氨基水杨酸维持治疗溃疡性结肠炎114例

目的:评估5-氨基水杨酸(5-ASA)对溃疡性结肠炎(UC)缓解期患者维持治疗及影响UC复发的相关因素.方法:回顾性分析2004-01/2010-08在北京大学第一医院消化内科就诊的114例缓解期UC患者的临床资料,纳入分析病例114例.其中,男64例,女50例,年龄16-76岁.结果:选择应用5-ASA诱导缓解治疗病例75例(65.8%).结果显示:(1)UC复发与性别无关;(2)病程>5年的UC患者复发率显著高于病程≤5年的UC患者(62.1%vs35.7%,P>0.05);(3)轻度UC患者5-ASA维持治疗剂量>2g/d者复发率显著低于≤2g/d者(10%vs33.3%,P<0.05);(4)轻度UC患者复发率显著低于中度和重度患者(24.6%vs83.3%,80.6%,P<0.05);(5)直肠型UC患者复发率(19.2%)较低;(6)诱导缓解治疗达到黏膜愈合患者的复发率显著低于未达到黏膜愈合的患者(4.8%vs89.6%,P<0.05);(7)UC患者诱导缓解后第2年始复发率随时间逐年上升.结论:黏膜愈合及疾病活动程度是影响UC复发率的重要因素,5-ASA是轻-中度UC维持缓解治疗的首选药物,5-...     

Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis （UC） diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram （ECG） revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram （ECHO） revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries （〈 3.5 mm）. Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.     

Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis

This 12-month, double-blind, placebo-controlled study randomized 205 ulcerative colitis patients in remission to placebo or controlled-release mesalamine at 4 g/day for 12 months. Patients were stratified to either pancolitis or left-sided disease, based on previous diagnosis. Maintenance of remission was defined as a sigmoidoscopic index of <5, less=" than=" five=" stools=" per=" day,=" and=" the=" absence=" of=" rectal=" bleeding.=" a=" significantly=" greater=" number=" of=" patients=" maintained=" remission=" on=" mesalamine=" 4=" g/day=" than=" on=" placebo=" at=" each=" of=" five=" study=" visits,=" following=" the=" first=" one-month=" visit=">P<0.05). the=" estimated=" 12-month=" remission=" rates=" for=" the=" mesalamine=" group=" were=" 64%=" (38%=" for=">P=0.0004). Baseline subgroups (disease location, time since last flare of active disease, and previous response to oral/rectal steroids or sulfasalazine) did not influence remission rates. Treatment-related adverse events were rare. Controlled-release mesalamine is a safe and efficacious single agent for maintaining remission of ulcerative colitis.The members of the Pentasa Study Group are as follows: Austin Diagnostic Clinic, Austin, Texas: Rambie L. Briggs, MD (Chief Investigator), V. Lawlis, MD, C. Felger, MD, G. Kitzmiller, MD, T. Liebermann, MD, Robert Frachtman, MD, Cindy Fischer, RN; San Francisco General Hospital, San Francisco, California: John P. Cello, MD (Chief Investigator), James Grendell, MD, Julie Satow, RN; University of Chicago School of Medicine, Chicago, Illinois: Stephen B. Hanauer, MD (Chief Investigator), Ira Hanan, MD, Pat Schultz, RN, Debbie James, RN; Nalle Clinic, Charlotte, North Carolina: James Mertesdorf, MD (Chief Investigator), Fitzgerald Hiestand, Jr., MD, Paul Tucker, Jr., MD, Thomas Roberts, MD, Pepper Brundage, CMA, Theresa Griffin, Medical Assistant, Janet E. Beck, CMA; Gastrointestinal Association, PA, Shawnee Mission, Kansas: Gregory Rick, Jr., MD (Chief Investigator), William Hartong, MD, William Buser, MD, Stanley Brand, MD, Peggy Bryant, RN, Michelle Kliewer, RN; HCA Presbyterian Hospital, Oklahoma City, Oklahoma: Malcolm Robinson, MD (Chief Investigator), Mark Mellow, MD, Robert McFadden, MD, David Neumann, MD, Karen Helin, Connie J. Privett-Cointepas, Rosemary R. Meek; Forsyth Medical Specialists, Winston-Salem, North Carolina: Walter Roufail, MD (Chief Investigator), Robert Brice, MD, Thomas P. Hughes, MD, Michael Fina, MD, Daniel Murphy, MD, Lacole Clinard, RN, Debbie Allman, Brenda Bowen; Northwest Gastroenterologists, Arlington Heights, Illinois: Jerrold L. Schwartz, MD (Chief Investigator), Igor Jurcik, MD, Loren B. White, MD, Michael Cohen, MD, David Sales, MD, PhD, Sandra Gochnour, RN, Nora M. York, RN; Digestive Healthcare, Minneapolis, Minnesota: David Weinberg, MD (Chief Investigator), Richard A. Dubow, MD, James Pries, MD, Joseph Tombers, MD, Stephen Gilberstadt, MD, Philip Hanna, MD, Mary Jane Watson, PharmD, Michele Mattison, LPN; Greater Cincinnati Gastroenterology Associates, Cincinnati, Ohio: Michael Safdi, MD (Chief Investigator), Alan Safdi, MD, Ronald Schneider, MD, George Waissbluth, MD, Michael D. Kraines, MD, Linda Magaw, CRC, Nancy Emrath, CRC; New England Medical Center, Boston, Massachusetts: Sanjeev Arora, MD, Marshall Kaplan, MD, Augusta McKusick, RN; Gastroenterology of Lake City, Waukegan, Illinois: Fred Rosenberg, MD (Chief Investigator), E.P. Kirch, MD, Hugh A. Allen, MD, Beth Weber, RN, Valley Health Care Medical Group, Binghamton, New York: Marcelo A. Barriero, MD (Chief Investigator), Leslie Bank, MD, Linda Gitchell, RN; Scripps Clinic Medicine Group, Inc, La Jolla, California: Williamson B. Strum, MD (Chief Investigator), Leona Goodman; University of Kansas Medical Center, Kansas City, Kansas: Philip Miner, MD (Chief Investigator), Steven Matter, MD, Dace Miller, MD, Clark Antonson, MD, Roland Christian, MD, Wendy Biddle, RN, Susan Clark, RN, Dorinda S. Sutton, RN; Oregon Health Sciences University, Portland, Oregon: Ronald M. Katon, MD (Chief Investigator), Fred Smith, MD, Kent Benner, MD, Emmet Keeffe, MD, David Lieberman, MD, Clifford Melnyk, MD, Flordeliz Lindenburg, Sue Webster; Medical College of Virginia, Richmond, Virginia: Alvin Zfass, MD, Donald Kirby, MD, Alfred Lee, MD, Yuen San Yee, MD, Paula Goshgarian-Patrick; Wake Research Associates, Raleigh, North Carolina: Charles Barish, MD, Philip Ashburn, MD, Diedrich C. Waterman, MD, Patricia M. Patterson, RN; Birmingham Gastroenterology Associates, Birmingham, Alabama: W. Roger Carlisle, MD (Chief Investigator), Leonard OuTim, MD, Raymond Tobias, MBChB, J. Lynn Cochran, MD, Walter J. Bristow, III, MD, Peter D. Miller, MD, Sarah Ingle, RN; Bowman-Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina: Robert M. Kerr, MD, Donald Castell, MD, Wallace C. Wu, MD, Joel E. Richter, MD, John H. Gilliam, III, MD, Greg Stark, PA; Marion Merrell Dow Inc., Kansas City, Missouri: Ruthanna Law, BSN, MA, Neil Malone, MA, Larry Roi, PhD, Michael Coen, MA, Doug Moore, BA, Mike McPherson, PharmD, MBA.     

5-氨基水杨酸锌胶囊治疗活动性溃疡性结肠炎的多中心随机双盲临床研究

目的 探索5-氨基水杨酸锌结肠溶胶囊治疗溃疡性结肠炎(活动期)的疗效、安全性及合适剂量.方法 采用多中心、随机、双盲双模拟、剂量反应和阳性对照设计,将2004年3月至9月上海瑞金医院等6家医院108例活动性溃疡性结肠炎患者随机分为5-氨基水杨酸锌高剂量组和低剂量组(每天给予5-氨基水杨酸锌结肠溶胶囊2次,每次分别为1 g和0.5 g)以及对照组(每天3次给予奥沙拉秦钠胶囊,每次1 g),每组36例,疗程均为8周.随访记录评估三组患者的临床症状和肠镜检查情况,并记录治疗过程中的不良反应.结果 5-氨基水杨酸锌高剂量组和低剂量组临床疗效有效率分别为68.97%和45.45%,对照组为62.86%,组间差异无统计学意义(P>0.05).肠镜检查5-氨基水杨酸锌高剂量组和低剂量组痊愈率分别为51.72%和21.21%,有效率分别为82.76%和69.70%,高剂量组优于低剂量组(P=0.023),但与对照组(分别为34.29%和88.57%)相比差异无统计学意义(P>0.05).不良反应主要是腹泻,5-氨基水杨酸锌高剂量组为2.8%(1/36),低剂量组未发生不良反应,对照组为2.8%(1/36).结论 5-氨基水杨酸锌高剂量组能有效治疗活动期溃疡性结肠炎,疗效与对照组相当,安全性相似,但试验药有减少用药次数的优点.     

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P<0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI –7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living. The results of this study suggest that 5-ASA foam may provide prompter remission of symptoms compared to liquid enema and it improves the quality of topical therapy in ulcerative colitis.This paper was presented in part at the Research Forum of the 92nd annual meeting of The American Gastrointestinal Association, New Orleans, May 18–24, 1991.The multicenter group included: M. Campieri, A. Belluzzi, G. Brunetti, P. Gionchetti, M. Miglioli, L. Barbara (Bologna); C. Prantera, A. Andreoli, E. Berto (Roma); P. Paoluzi, M.C. Di Paolo, A.O. Paoluzi (Roma); F. Pallone, F. Luzza (Catanzaro); M. Cottone, L. Oliva (Palermo); G. Bianchi Porro, S. Ardizzone, M. Petrillo (Milano); G. D'Albasio, G. Trallori (Firenze); G.C. Sturniolo, M.C. Montino (Padova); A. Pera, C. Barletti (Torino); R. de Franchis, G. Grandinetti, G.M. Meucci, M. Vecchi (Milano); P. Bianchi, M.C. Campanini, T. Ranzi (Milano); L. Capurso, C. Papi (Roma).Supported by a grant from Bracco and Giuliani (Milan, Italy).     

Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses

BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.     

A prospective randomized double blind trial comparing prednisolone and 4-aminosalicylic acid enemas in acute distal ulcerative colitis

A prospective double blind and randomized study was conducted to compare 4-aminosalicylic acid (4-ASA) and prednisolone-21-phosphate enemas in inducing remission in patients with acute distal ulcerative colitis. Patients with ulcerative colitis distal to the splenic flexure as assessed by flexible colonoscopy, barium enema and histology were included in the study. Of 40 consecutive patients, 20 were randomized to each of the two treatment groups. Clinical evaluation was done weekly; sigmoidoscopy and histology were performed at entry and at the end of 4 weeks. Therapy was discontinued in four patients treated with prednisolone enemas due to worsening of symptoms. The clinical improvement was significant in the remaining patients (P less than 0.001) and was similar in the two groups (P greater than 0.1). Sigmoidoscopic and histological improvement were better with 4-ASA than with prednisolone enemas. No adverse effects were observed in any of the patients treated. The present study suggests that 4-ASA is a safe and effective treatment for inducing remission in acute distal ulcerative colitis.     

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.     

Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.