Experience with topical administration of 4-aminosalicylic acid in ulcerative colitis

4-Aminosalicyclic acid was applied topically in a daily dose of 1.4 gm for two weeks in ten patients with ulcerative colitis. After favorable results, the therapeutic effects of 4-aminosalicylic acid and salazopyrin enemas were compared in a two-week cross-over open trial, in 20 patients suffering from recurrent ulcerative colitis involving the rectum and rectosigmoid. No significant difference was found in the changes of the endoscopic picture of the mucosa. The results did not show a significant difference between 4-aminosalicylic acid and salazopyrin enemas, either in the clinical activity or in the histologic picture. 4-Aminosalicylic acid seems to be a suitable drug for improving the clinical symptoms of ulcerative proctitis.     

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.     

Recent advances in the endoscopic assessment of ulcerative colitis

Endoscopic assessment of the severity and extent of inflammation as well as the presence of neoplastic lesions is integral to the management of ulcerative colitis (UC). Numerous scoring systems to assess endoscopic severity indicate that a perfect scoring system is still lacking. Many of the scoring systems were designed in the era of standard-definition white-light endoscopy. The resolution and details provided by the new-generation endoscopes and high-definition equipment of both mucosal pattern and vascular pattern mandates a fresh look at endoscopic scoring in UC. In this context, we describe some of the scoring systems recently designed using novel endoscopic techniques. Current definitions of mucosal healing do not completely reflect histologic healing but this gap is being closed rapidly by novel endoscopic techniques with high-definition images that can be optically and digitally enhanced. The best technique to detect dysplasia in UC is still widely debated. New endoscopic resection techniques may now be able to limit the number of colectomies that need to be performed in the presence of dysplasia owing to improvement in performing local resection.     

5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis

AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study included 130 inflammatory bowel disease(IBD)patients receiving 5-ASA as pH-dependent-release formulations(73 patients),time-dependent-release formulations(11 patients),or pro-drugs(18patients).In addition,28 patients were receiving topical treatment(2-4 g/d)with pH-dependent-release formulations.Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy.The 5-ASA concentrations(ng/mg)were measured in tissue homogenatesusing high-pressure liquid chromatography with electrochemical detection.The t test and Mann-Whitney test,when appropriate,were used for statistical analysis.RESULTS:Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA(51.75±5.72 ng/mg)compared with patients receiving pro-drugs(33.35±5.78 ng/mg,P=0.01)or time-dependent-release formulations(38.24±5.53 ng/mg,P=0.04).Patients with endoscopic remission had significantly higher mucosal concentrations of5-ASA than patients with active disease(60.14±7.95ng/mg vs 35.66±5.68 ng/mg,P=0.02).Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation(67.53±9.22 ng/mg vs 35.53±5.63 ng/mg,P<0.001).Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone(72.33±11.23 ng/mg vs 51.75±5.72 ng/mg,P=0.03).CONCLUSION:IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation,and the highest mean concentration was achieved using pH-dependent-release formulations.     

国产5-氨基水杨酸肠溶片治疗溃疡性结肠炎多中心临床研究

目的　评价国产 5 氨基水杨酸 (5 ASA)肠溶片治疗溃疡性结肠炎 (UC)的疗效和安全性及该药的口服吸收情况。方法　采用多中心、随机、双盲、双模拟和对照方案 ,将 1 2 9例UC患者随机分为5 ASA肠溶片试验组 (6 5例 ,2 .4 g/d)和水杨酸偶氮磺胺吡啶 (SASP)对照组 (6 4例 ,4 .0g/d) ,疗程均为6周。治疗第 8天 ,随机抽取试验组 1 3例和对照组 1 2例UC患者血清 ,应用高效液相色谱分析法检测血清 5 ASA及其代谢产物Ac 5 ASA的稳态血药浓度。对两组患者治疗前后的临床症状、粪便检查和肠镜检查的情况进行比较 ,并记录治疗过程中的不良反应。结果　实际完成研究者 1 2 0例 (5 ASA组 6 1例 ,SASP组 5 9例 ) ,两组各有 4例失访 ,SASP组有 1例因严重胃肠道不良反应中途退出。 5 ASA肠溶片组和SASP组治疗UC的总有效率分别为 70 .0 5 %和 6 7.79% ,两组间差异无显著性 (P >0 .0 5 ) ,5 ASA肠溶片的完全缓解率明显高于SASP (2 9.5 1 %比 1 3.31 % ,P <0 .0 5 )。 5 ASA肠溶片组和SASP组的不良反应分别为 1 1 .4 8%和 2 3.33%。 5 ASA组和SASP组的血清 5 ASA浓度分别为 (0 .0 32± 0 .0 0 8) μg/ml和 (0 .0 4 1± 0 .0 0 5 ) μg/ml(P >0 .0 5 )。 结论　 5 ASA肠溶片治疗UC总有效率与SASP相仿 ,但对UC的完     

Duration of treatment with 5-aminosalicylic acid compounds

The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis,but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962,the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973,the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However,in 1985,a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.     

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.     

溃疡性结肠炎患者白细胞介素-6活性研究

目的探讨白细胞介素-6(IL-6)在溃疡性结肠炎(UC)中的表达水平.方法以外周血单核细胞(PBMC)体外培养诱生IL-6.以B9细胞与培养液共育,测定IL-6水平,将健康人(HC)与UC患者进行比较研究,其中HC组20例,UC组25例(静止期与轻、中、重组,例数分别为5、10、6、4例).结果UC组与对照组IL-6活性分别为(261.48±82.01)U/ml和(100.00±57.65)U/ml,两者差异有非常显著性(P＜0.001).UC组静止期与轻、中、重三组比较IL-6活性依次为(121.06±43.00)U/ml、(240.23±61.60)U/ml、(275.83±78.40)U/ml及(315.00±142.92)U/ml,P值分别小于0.02、0.02及0.1.而静止期与对照组相比差异无显著性(P＞0.05).按病变累及范围,全结肠组与左半结肠组IL-6活性分别为(312.33±107.34)U/ml和(244.88±69.97)U/ml,两组间差异无显著性(P＞0.05).结论UC活动期患者IL-6活性明显高于对照与静止期患者,且随病情加重呈上升趋势.IL-6活性与病变累及范围无关.``     

“Mucosal healing” in ulcerative colitis:Between clinical evidence and market suggestion

In recent decades,the prominent role of endoscopy in the management of ulcerative colitis(UC)has been translated into the concept of mucosal healing(MH)as a fundamental therapeutic end-point.This is partially the consequence of growing evidence of a positive prognostic role of MH on the disease course and partially due to market cues indicating a higher rate of MH in patients treated by novel potent biologic agents.The aim of the present review is to clarify the current knowledge of MH in UC,analyzing the definition,the putative prognostic role and the association of MH with the current drugs used to treat UC patients.Because solid data about the management of UC patients based solely on the healing of the mucosa are not yet available,a tailored approach for individual patients thatconsiders the natural history of UC and the presence of prognostic indicators of aggressive disease is desirable.Consequently,unnecessary examinations and treatment would be avoided and restricted to UC patients who require the maximum amount of effort to affect the disease course in the short and long term.     

Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis

Proinflammatory cytokines are believed to be involved in the pathogenesis of ulcerative colitis (UC). The aim of this study was to clarify the profiles of proinflammatory cytokine production in patients with UC in terms of disease intractability, endoscopic findings, and host response to lipopolysaccharide (LPS) stimulation. Colonic mucosal tissues were obtained from patients with active UC (n = 15, including 4 patients with intractable disease) and inactive UC (n = 7), non-inflammatory bowel disease (IBD) colitis (n = 11), and controls (n = 20). Organ culture was performed, and the amounts of four cytokines (described below) in the culture media were determined by enzyme-linked immunosorbent assay (ELISA). LPS stimulation enhanced interleukin (IL)-1β, IL-8, and IL-6 production in colonic specimens from all groups, but enhanced tumor necrosis factor (TNF)-α production only in active UC specimens. Levels of IL-6, IL-8, and TNF-α were significantly higher in active UC than in non-IBD colitis, and the production of all three of these cytokines was correlated to the endoscopic grade of inflammation. The production of these cytokines was also significantly higher in patients with intractable disease receiving corticosteroids than in patients with non-intractable disease receiving corticosteroids. These results suggest that enhanced production of mucosal proinflammatory cytokines may be implicated in the pathogenesis of UC. (Received Jan. 30, 1998; accepted Aug. 28, 1998)     

Colon-specific prodrugs of 4-aminosalicylic acid for inflammatory bowel disease

Despite the advent of biological products,such as antitumor necrosis factor-αmonoclonal antibodies(infliximab and adalimumab),for treatment of moderate to severe cases of inflammatory bowel disease(IBD),most patients depend upon aminosalicylates as the conventional treatment option.In recent years,the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin,omega-3 fatty acids,probiotics and innovative formulations such as high-dose,oncedaily multi-matrix mesalamine,which are designed to minimize the inflammatory process through inhibition of different targets.Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid(ASA)in the form of sulfasalazine,balsalazide,olsalazine and ipsalazine,but rarely for its positional isomer 4-ASA-a wellestablished antitubercular drug that is twice as potent as 5-ASA against IBD,and more specifically,ulcerativecolitis.The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD.The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.     

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.     

Mucosal vascular pattern in ulcerative colitis: observations using narrow band imaging colonoscopy with special reference to histologic inflammation

Background and aim  Narrow band imaging (NBI) is a novel endoscopy system, which enables a clear visualization of the mucosal vasculature of the gastrointestinal tract. The aim of this study is to determine whether this system may be of value for assessing the disease severity in ulcerative colitis (UC). Materials and methods  We observed the mucosal vascular pattern (MVP) in 157 colorectal segments of 30 patients with UC using both conventional and NBI colonoscopy. The MVP was determined to be normal or distorted under conventional colonoscopy and, subsequently, to be clear or obscure under NBI colonoscopy. The histologic variables in each segment were assessed in biopsy specimen. The possible correlation between MVP and the histologic grade of inflammation was evaluated. Results  The MVP under conventional colonoscopy was normal in 60 segments while it was distorted in 97 segments. In all of the former 60 segments, their MVP was clear under NBI colonoscopy. The MVP in the latter 97 segments were determined to be clear (n = 44) or obscure (n = 53) under NBI colonoscopy. Acute inflammatory cell infiltrates (26% vs. 0%, p = 0.0001), goblet cell depletion (32% vs. 5%, p = 0.0006), and basal plasmacytosis (2% vs. 21%, p = 0.006) were more frequently observed in segments with an obscure MVP than in those with a clear MVP. Conclusion  NBI colonoscopy may be of value for determining the grade of inflammation in patients with quiescent UC.     

Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission

BackgroundIt has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission.MethodsPatients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005–2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated.ResultsOne hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15–56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P = 0.048) or together with a past flare within the previous 12 months (P = 0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR = 7.5; IC95%; 1.8–29.9; P = 0.005).ConclusionsIn UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.     

5-ASA in ulcerative colitis： Improving treatment compliance

5-aminosalicylic acid （5-ASA） compounds are a highly effective treatment for ulcerative colitis （UC）. While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix （MMx） is a novel, high strength （1.2 g）, oral formulation designed for oncedaily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA （Asacol）, even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.     

Mucosal inflammation in the terminal ileum of ulcerative colitis patients: Endoscopic findings and cytokine profiles

BACKGROUND: Currently, published reports of mucosal inflammation in the terminal ileum of ulcerative colitis (UC) before colectomy are scarce. AIM: To investigate inflammation in the terminal ileum of UC patients by endoscopic examinations and measurement of mucosal cytokine profiles. METHODS: Fifty consecutive patients with active UC were studied. At ileocolonoscopy, mucosal biopsies were taken from the terminal ileum. As control, mucosal biopsies from 20 patients without inflammation were examined. RESULTS: Thirty-eight patients showed endoscopically normal terminal ileum, four showed backwash ileitis, and eight showed non-backwash ileitis (ileitis with normal caecum). Pancolitis was observed in all of four patients with backwash ileitis, in 4 of 8 (50%) with non-backwash ileitis, and in 4 of 38 (11%) without ileal inflammation (P=0.0002). Extraintestinal manifestations were observed in none of 4 patients with backwash ileitis, in 6 of 8 (75%) with non-backwash ileitis, and in 3 of 38 (8%) without ileal inflammation (P<0.0001). In patients with backwash ileitis and non-backwash ileitis, ileal interleukin [IL]-1beta, IL-6, IL-8 and tumour necrosis factor-alpha levels were significantly elevated compared with the control group. Only extraintestinal manifestation was associated with higher ileal cytokine levels, whereas age, sex, and duration, extent and severity of UC did not show any apparent association. CONCLUSIONS: In patients with backwash ileitis, elevated ileal cytokines might reflect a reaction to regurgitation of colonic content into the ileum, but in patients without backwash ileitis, alternative factors are expected to contribute to the aetiology of ileal inflammation. Patients with extraintestinal manifestations had elevated ileal cytokine levels.     

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.