A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. 5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. 5-Aminosalicylic acid enemas in treatment of distal ulcerative colitis and proctitis in Canada Effect of weekend 5‐aminosalicylic acid (mesalazine) enema as maintenance therapy for ulcerative colitis: Results from a randomized controlled study Trial of trefoil factor 3 enemas, in combination with oral 5‐aminosalicylic acid, for the treatment of mild‐to‐moderate left‐sided ulcerative colitis Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study Quality of Life Improvements Attributed to Combination Therapy with Oral and Topical Mesalazine in Mild-to-Moderately Active Ulcerative Colitis Mesalamine Foam Enema Versus Mesalamine Liquid Enema in Active Left-Sided Ulcerative Colitis Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation Rebamipide Enemas–New Effective Treatment for Patients with Corticosteroid Dependent or Resistant Ulcerative Colitis Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group. Clinical trial: randomized‐controlled clinical study comparing the efficacy and safety of a low‐volume vs. a high‐volume mesalazine foam in active distal ulcerative colitis Effect of Budesonide Enema on Remission and Relapse Rate in Distal Ulcerative Colitis and Proctitis Controlled, open, randomized multicenter trial comparing the effects of treatment on quality of life, safety and efficacy of budesonide foam and betamethasone enemas in patients with active distal ulcerative colitis. Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis 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 Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-γ Activity Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee Bioavailability and therapeutic activity of alicaforsen (ISIS 2302) administered as a rectal retention enema to subjects with active ulcerative colitis Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double‐blind, randomized, placebo‐controlled study A randomized trial of nicotine enemas for active ulcerative colitis. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. Mesalazine (5-aminosalicylic acid) suppositories in the treatment of ulcerative proctitis or distal proctosigmoiditis. A randomized controlled trial. 4-Aminosalicylic acid retention enemas in treatment of distal colitis Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: a multicenter, randomized, double-blind study. Incidence and Prevalence of Inflammatory Bowel Disease in a Northern California Managed Care Organization, 1996–2002 Local application of tacrolimus in distal colitis: Feasible and safe Treatment of left-sided ulcerative colitis with 4-aminosalicylic acid enemas. A double-blind, placebo-controlled trial. A Phase II dose ranging, double‐blind, placebo‐controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left‐sided ulcerative colitis Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis. Oral versus combination mesalazine therapy in active ulcerative colitis: a double‐blind, double‐dummy, randomized multicentre study A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis. Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis Is topical therapy necessary in acute distal colitis? Double‐blind comparison of high‐dose oral mesalazine versus steroid enemas in the treatment of active distal ulcerative colitis Clinical trial: A novel high‐dose 1 g mesalamine suppository (salofalk) once daily is as efficacious as a 500‐mg suppository thrice daily in active ulcerative proctitis 5-Aminosalicylic acid enemas: effective agent in maintaining remission in left-sided ulcerative colitis. Topical Treatment of Distal Active Ulcerative Colitis With Beclomethasone Dipropionate or Mesalamine: A Single-blind Randomized Controlled Trial Budesonide Foam vs. Hydrocortisone Acetate Foam in the Treatment of Active Ulcerative Proctosigmoiditis Topical treatment of distal ulcerative colitis with 4-amino-salicylic acid enemas. A randomised, controlled, double blind, escalating dose study of alicaforsen enema in active ulcerative colitis
BACKGROUND / AIMS Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration . The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed . METHODS Steroid and mesalamine enemas were withdrawn before the study . Forty patients were assigned to 1 of 4 strata : no concomitant therapy , oral steroids , oral salicylates , or oral steroids and salicylates . After stratification , patients were r and omized to nightly treatment with 350 mg cyclosporine ( n = 20 ) or placebo ( n = 20 ) enemas . Clinical response was determined at baseline and 4 weeks by endoscopy , physician assessment , and a patient diary of daily symptoms . Trough blood cyclosporine levels were measured by high-performance liquid chromatography . RESULTS At 4 weeks , 8 of 20 patients ( 40 % ) who received cyclosporine showed clinical improvement compared with 9 of 20 patients ( 45 % ) who received placebo . One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine , and another patient receiving cyclosporine was unable to tolerate the enema vehicle . No other toxicity was noted during the trial . Blood cyclosporine levels were detectable in only two patients . CONCLUSIONS Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Thirty patients with distal ulcerative colitis in remission ( 17 proctitis , 13 proctosigmoiditis ) were r and omly given either 5-aminosalicylic acid ( 5-ASA ) or placebo suppositories , 400 mg bid . During the 1-yr follow-up , patients were assessed clinical ly 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 The efficacy and safety of 4 g 5-aminosalicylic acid ( 5-ASA ) enemas were assessed in 59 patients with ulcerative colitis involving up to 50 cm of their distal colon . Twenty-nine patients received  5-ASA  and 30 received a placebo . There were 12 dropouts ( five in the active and seven in the placebo group ) during the study because of insufficient efficacy . After six weeks of therapy , 63 % of the patients receiving the 5-ASA were considered to be “ much improved ” by the study physician compared to 20 % patients on placebo ( P<0.0001 ) . A disease activity index ( DAI ) , based upon patient symptoms and sigmoidoscopic appearance , was used to assess efficacy . Mean DAI declined 75 % for patients on 5-ASA enemas and 32 % for patients on placebo ( P<0.05 ) . The 5-ASA enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Background : 5‐Aminosalicylic acid ( 5‐ASA ) is known to be effective in the treatment of active ulcerative colitis ( UC ) . The aim of the current study was to investigate the effect of 5‐ASA enemas , as a maintenance therapy for UC , when administered twice weekly as a weekend treatment regimen , compared to daily oral 5‐ASA alone . We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school . Methods : Between January 2004 and August 2005 , patients with UC , in whom remission of the condition had just been induced , were r and omly assigned to either : the weekend 5‐ASA enema group ( n = 11 ) , who received 1 g 5‐ASA enemas twice a week on Saturday and Sunday plus oral 5‐ASA 3 g/day for 7 days , or to the daily oral 5‐ASA use only group ( n = 13 ) , who received only oral 5‐ASA 3 g/day for 7 days . The primary endpoint of the study was defined as the incidence of relapse . The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5‐ASA enema group . Results : In the weekend enema group , 2 patients ( 18.2 % ) had relapses compared with 10 ( 76.9 % ) in the oral 5‐ASA only group . The multivariate hazard ratio of relapse associated with weekend 5‐ASA enema , relative to the oral alone group , was 0.19 ( 95 % confidence interval , 0.04–0.94 ) . Conclusions : This study demonstrated the beneficial effects of adding weekend 1 g 5‐ASA enema to daily 3 g oral 5‐ASA as maintenance therapy for UC Background : Current treatment of ulcerative colitis is imperfect . Trefoil peptides are known to stimulate repair in many models of injury , including animal models of colitis Background and aims : Oral aminosalicylates are well established in the treatment of active mild/moderate ulcerative colitis ( UC ) when the disease is extensive ( that is , beyond the splenic flexure ) . The majority of clinical symptoms relate to disease activity in the distal part of the colon and therefore this study was design ed to investigate if adding a mesalazine enema to oral mesalazine has additional benefit for patients with extensive mild/moderate active UC . Methods : A r and omised double blind study was performed in 127 ambulatory patients . All received 4 g/day ( twice daily dosing ) oral mesalazine for eight weeks . During the initial four weeks , they additionally received an enema at bedtime containing 1 g of mesalazine or placebo .  Disease activity was assessed using the ulcerative colitis disease activity index , with clinical and endoscopic signs at four and eight weeks . Results : Remission was obtained in 44 % ( 95 % confidence interval ( CI ) 31 % , 58 % ) of the mesalazine enema group ( Me ) and in 34 % ( 95 % CI 21 % , 49 % ) of the placebo enema group ( Pl ) at four weeks ( p = 0.31 ) and in 64 % ( 95 % CI 50 % , 76 % ) of the Me group versus 43 % ( 95 % CI 28 % , 58 % ) of the Pl group at eight weeks ( p = 0.03 ) . Improvement was obtained in 89 % ( 95 % CI 78 % , 96 % ) of the Me group versus 62 % ( 95 % CI 46 % , 75 % ) of the Pl group at four weeks ( p = 0.0008 ) and in 86 % ( 95 % CI 75 % , 94 % ) of the Me group versus 68 % ( 95 % CI 53 % , 81 % ) of the Pl group at eight weeks ( p = 0.026 ) . Conclusion : In patients with extensive mild/moderate active UC , the combination therapy is superior to oral therapy . It is safe , well accepted , and may be regarded as firstline treatment Background / Aim : To investigate patient-reported  health-related quality of life ( HRQoL ) in data collected from a multinational r and omized double-blind controlled trial comparing oral mesalazine ( 4 g ) + topical mesalazine enema ( 1 g ) to oral mesalazine alone ( 4 g ) . Methods : HRQoL was collected using the EQ-5D at baseline and weeks 2 , 4 and 8 . The EQ-5D assesses mobility , self-care , usual activities , pain/discomfort and anxiety/depression . Scores from each dimension were reported individually , and converted into a weighted health state which reflects an individual ’s perception of their health condition . Results : At week 4 , a significant HRQoL improvement was observed for patients on mesalazine enemas compared to placebo enemas , with EQ-5D scores of 0.906 and 0.838 , respectively ( p < 0.05 ) . Mesalazine enema was found to reduce the probability of impairment at week 4 for mobility ( p = 0.049 ) and anxiety/depression ( p = 0.048 ) , and was of borderline significance for pain/discomfort ( p = 0.053 ) ; there was also an increased probability of influencing HRQoL changes for mobility ( p < 0.005 ) , usual activities ( p < 0.005 ) , pain/discomfort ( p < 0.005 ) and anxiety/depression ( p < 0.005 ) , based on reported HRQoL problems at baseline . Conclusions : Including 1 g mesalazine enemas with 4 g oral mesalazine significantly improved HRQoL  in patients with active ulcerative colitis . The improvement in QoL of patients with UC preceded clinical remission , and this underlines the importance of including QoL instruments in clinical studies AIM : To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis ( UC ) . METHODS : In a multicenter investigator-blind trial , 375 patients with mild-to-moderate UC were r and omized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk ( W ) . Inclusion criteria were : disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index ( CAI ) 1–4 ≥ 4 . Primary end point was clinical remission at W4 defined as a CAI 1–4 ≤ 2 . Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5 % unilateral confidence interval ( 97.5 % CI ) of the difference in remission rates between foam and liquid enema groups was greater than −15 % . RESULTS : Remission rates at W4 in foam versus liquid were 68.3 % versus 73.6 % in per protocol ( PP ) population ( lower limit of 97.5 % CI −15.1 % ) and 66.7 % versus 70.5 % in intention-to-treat ( ITT ) population ( 97.5 % CI −13.4 % ) . Remission rates at W2 were 48.1 % versus 50.6 % in ITT ( 97.5 % CI −12.8 % ) and 49.1 % versus 52.1 % in PP ( 97.5 % CI −13.8 % ) in foam versus liquid , respectively . Both treatments were well tolerated . CONCLUSIONS : A 4-wk treatment of 1 g mesalamine foam  induced a clinical remission in 68 % patients versus 73 % with 1 g mesalamine liquid enema . Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis , it was achieved in the ITT population and at W2 in both population s. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum ( < 20 cm ) entered the trial . Thirty-two were treated with 5-ASA 500 mg suppositories ( Asacol ) 3 times a day for 1 month while 30 received a placebo given in the same regime . Clinical , sigmoidoscopic and histological assessment was carried out before , after 15 days and after 1 month of treatment . At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo ( p<0.01 ) . There were no unwanted effects related to the use of suppositories . This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis In this study we investigated the effect of rebamipide enema in patients with steroid-resistant and /or dependent ulcerative colitis .  Rebamipide enemas were administered twice daily for a 12-week period ; this treatment was further continued longer in patients who requested this . Disease activity index as reflecting the clinical condition and endoscopic index with histological grading were determined before and after the treatment period . Nine of 11 ( 81.8 % ) patients on 12-week treatment with rebamipide approved and were classified as colitis in remission . Moreover , seven of 11 patients requested long-term medication , the longest medication term being 80 weeks . These results medicated that rebamipide enemas may be effective in patients with steroid-resistant and /or dependent ulcerative colitis BACKGROUND & AIMS Budesonide is a highly potent topical glucocorticosteroid that is characterized by low systemic availability as a result of high first-pass hepatic metabolism . The aim of this study was to evaluate the efficacy and safety of three doses of an enema preparation of budesonide in patients with active distal ulcerative colitis/proctitis . METHODS In a double-blind multicenter trial , 233 patients were r and omized to receive either a  placebo enema or budesonide enema at a dose of 0.5 mg/100 mL , 2.0 mg/100 mL , or 8.0 mg/100 mL. The primary efficacy variables were an improvement of sigmoidoscopic inflammation grade , total histopathology score , and remission rates . Effects on cortisol concentrations were also assessed . RESULTS After 6 weeks of treatment , there was significant improvement in sigmoidoscopy and histopathology scores in the budesonide 2.0-mg and 8.0-mg dose groups compared with placebo .  Remission was achieved in 19 % of patients in the 2.0-mg budesonide group ( P < /= 0.050 ) and 27 % of patients in the 8.0-mg budesonide group ( P < /= 0.001 ) compared with 4 % in the placebo group . More than 90 % of all budesonide patients had a normal adrenocorticotropin (ACTH)-stimulated cortisol response at the last visit . The budesonide enemas were well tolerated . CONCLUSIONS Budesonide enema is both effective and safe for the treatment of active distal ulcerative colitis/proctitis . A dose of 2 . 0 mg/100 mL budesonide is the lowest effective dose Background Rectally administered mesalazine ( mesalamine ; 5‐aminosalicylic acid ) is the first‐line therapy for treatment of distal ulcerative colitis . Recently , a high‐volume 5‐aminosalicylic acid foam has been shown to be as effective and safe as st and ard 5‐aminosalicylic acid enema Background : Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis ( UC ) . With the introduction of budesonide , the risk of systemic side effects may be reduced . We investigated whether budesonide enema , 2 mg/100 ml , administered twice daily ( b.i.d . ) could increase the remission rate in comparison with the once daily ( o.d . ) st and ard regimen . Furthermore , we evaluated whether 2 mg budesonide enema , given twice weekly , could have a relapse preventing effect . Methods : 149 patients with active distal UC were treated in a controlled , double-blind multicentre study with two parallel groups : placebo enema in the morning and budesonide enema in the evening ( i.e. 2 mg/day ) or budesonide enema b.i.d . ( i.e. 4 mg/day ) until remission ( absence of clinical symptoms and endoscopic healing ) or at most 8 weeks . Patients in remission were r and omized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse . Results : The remission rates at 4 weeks were 33 % for o.d . and 41 % for b.i.d . regimens ( NS ) and correspondingly 51 % and 54 % at 8 weeks ( NS ) . The b.i.d . group had an increased frequency of impaired adrenal function , 32 % versus 4.8 % ( P = 0.001 ) . The relapse rates during maintenance treatment with budesonide enema and placebo were 15 % versus 24 % after 8 weeks , 31 % versus 27 % after 16 weeks and 41 % versus 51 % after 24 weeks ( NS ) . Conclusion : Budesonide enema 2 mg o.d . appears to be the optimal dosage in active distal UC . We could not show that budesonide enema twice weekly is sufficient to maintain remission BACKGROUND / AIMS There is evidence of a higher quality of life with foams as compared with enemas . The purpose of this study was to assess the effect of treatment with budesonide foam or betamethasone enema on the quality of life and the clinical outcome in patients with distal ulcerative colitis . METHODOLOGY In an open multicenter trial , patients with active distal ulcerative colitis were r and omized to receive 2 mg/50 mL budesonide foam or 5 mg/100 mL betamethasone enema . Primary outcome variable was the change in the mean Life Quality Index . Therapeutic efficacy was determined by clinical activity , endoscopical and histological indices . RESULTS 38 patients were included in the study . The decrease of the mean Life Quality Index was more pronounced in the budesonide group . No significant difference in the efficacy of treatment was observed for both groups . Betamethasone  suppressed the plasma cortisol level in the majority of the patients ( 87 % ) compared to only 22 % of the patients receiving budesonide . CONCLUSIONS The quality of life is not significantly different in patients during treatment with budesonide foam or betamethasone enema for active distal ulcerative colitis . However , while having comparable clinical efficacy budesonide foam has less effect on the plasma cortisol level thus potentially minimizing steroid side effects 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 r and omized 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 ≥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≤ 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 Background —Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis . Maintenance of remission with lower doses would be an advantage . Aim —The efficacy of mesalazine suppositories ( Pentasa ) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied . Methods —Ninety five patients with cryptogenetic proctitis were r and omised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa  ( n=48 ) or placebo ( n=47 ) . In the case of a relapse , the patients received one suppository/day . Results —It was found that 25 of 48 subjectsv 18 of 47 remained in remission in the mesalazine and placebo groups respectively . The relapse rate was lower in the mesalazine 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 0–365 days ( 48 % v 62 % , p=0.18 ) . Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively ( p=0.001 ) . Overall , 61%v 28 % patients remained in the protocol and were in remission at one year ( p=0.001 ) . Tolerance was good . Conclusion —Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis . Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed OBJECTIVES : Impaired epithelial expression of peroxisome proliferator-activated receptor-γ ( PPARγ ) has been described in animal colitis models and briefly in patients with ulcerative colitis , but the functional significance in humans is not well defined . We examined PPARγ expression and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone ( a PPARγ lig and ) in patients with ulcerative colitis . METHODS : Spontaneous and rosiglitazone-mediated PPARγ and adipophillin expression ( a gene transcriptionally activated by PPARγ ) were measured by reverse transcriptase PCR in colonic biopsies and isolated epithelial cells from patients with ulcerative colitis and controls . Fourteen patients with active distal ulcerative colitis were r and omized to either rosiglitazone ( 4 mg ) or mesalazine ( 1 g ) enema treatment once daily for 14 days . RESULTS : PPARγ expression was fourfold reduced in epithelial cells from inflamed compared with uninflamed mucosa and controls . Adipophillin levels were decreased in parallel . Rosiglitazone induced a concentration-dependent increase in adipophillin levels and restored PPARγ activity in epithelial cells from inflamed mucosa in vitro . Rosiglitazone enema treatment was well tolerated and reduced the Mayo ulcerative colitis score from 8.9 to 4.3 ( P<0.01 ) , similar to the effect of mesalazine . Rosiglitazone  increased adipophillin levels in the epithelial cells of the patients , indicating PPARγ activation in vivo . CONCLUSIONS : Roziglitasone enemas improve impaired PPARγ activity in inflamed colonic epithelium and have beneficial clinical effect in patients with active distal ulcerative colitis . These findings raise interest in further studies of PPARγ lig and s that exhibit their anti-inflammatory effect locally in the gut to avoid possible systemic side effects Guidelines for clinical practice are aim ed to indicate preferred approaches to medical problems as established by scientifically valid research . Double-blind placebo controlled studies are preferable , but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine . When only data that will not withst and objective scrutiny are available , a recommendation is identified as a consensus of experts . Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aim ed to indicate the preferable but not necessarily the only acceptable approach to a specific problem . Guidelines are intended to be flexible and must be distinguished from st and ards of care , which are inflexible and rarely violated . Given the wide range of specifics in any health-care problem , the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision . Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees . Each has been intensely review ed and revised by the Committee , other experts in the field , physicians who will use them , and specialists in the science of decision analysis . The recommendations of each guideline are therefore considered valid at the time of composition based on the data available . New developments in medical research and practice pertinent to each guideline will be review ed at a time established and indicated at publication to assure continued validity . The recommendations made are based on the level of evidence found . Grade A recommendations imply that there is consistent level 1 evidence ( r and omized controlled trials ) , grade B indicates that the evidence would be level 2 or 3 , which are cohort studies or case – control studies . Grade C recommendations are based on level 4 studies , meaning case series or poor- quality cohort studies , and grade D recommendations are based on level 5 evidence , meaning expert opinion Alicaforsen is a phosphorothioate‐modified antisense oligodeoxynucleotide design ed to sequence‐specifically reduce intercellular adhesion molecule 1 messenger RNA levels Rectal formulations of mesalazine are the treatment of choice in mildly to moderately active ulcerative colitis . A new foam formulation of mesalazine was developed to improve both drug delivery and patient acceptance BACKGROUND & AIMS Ulcerative colitis ( UC ) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events ( AEs ) . Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC . METHODS We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a r and omized double-blind study . Patients continued their oral therapy , if any , for UC : 68 patients were taking mesalamine , 15 patients were taking prednisolone , and 12 patients were taking thiopurines during the study .  Clinical , sigmoidoscopic , and histologic assessment s were made at baseline and at the end of the study and symptoms were recorded daily on a diary card . The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index . After the study , patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated . AEs and salivary cotinine levels were monitored throughout the study . RESULTS Clinical remission was achieved in 14 of 52 ( 27 % ) patients on active treatment and 14 of 43 ( 33 % ) patients on placebo ( P = .55 ) . The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo ( P = .88 ) . Only 1 patient discontinued treatment because of an AE ( abdominal pain ) . In the 47 patients taking mesalamine only , active treatment conferred benefit that was not statistically significant ; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo ( P = .20 ) . CONCLUSIONS Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC BACKGROUND Epidermal growth factor ( EGF ) is a potent mitogenic peptide produced by salivary gl and s. We examined whether EGF enemas are an effective treatment for active left-sided ulcerative colitis and ulceration limited to the rectum ( proctitis ) . METHODS In a r and omized , double-blind clinical trial conducted at Leicester Royal Infirmary , 12 patients with mild-to-moderate left-sided ulcerative colitis received daily enemas of 5 microg of EGF in 100 ml of an inert carrier and 12 received daily enemas with carrier alone for 14 days . All also began to receive 1.2 g of oral mesalamine per day or had their dose increased by 1.2 g per day . Patients were assessed clinical ly at 0 , 2 , 4 , and 12 weeks and by  sigmoidoscopy and biopsy  at 0 , 2 , and 4 weeks . The primary end point was disease remission ( defined by a St. Marks score of 4 or less without sigmoidoscopic evidence of inflammation ) at two weeks . Secondary end points were clinical ly significant improvements in disease activity ( defined by a decrease of more than 3 points in the St. Marks score or the ulcerative colitis disease-activity index ) at two and four weeks . Analyses were performed according to the intention-to-treat principle . RESULTS After two weeks , 10 of the 12 patients given EGF enemas were in remission , as compared with 1 of 12 in the control group ( 83 percent vs. 8 percent , P<0.001 ) . At the 2-week assessment , disease-activity scores , sigmoidoscopic score , and histologic scores were all significantly better in the EGF group than in the placebo group ( P<0.01 for all comparisons ) , and this benefit was maintained at 4 weeks and at 12 weeks . CONCLUSIONS This study provides preliminary data suggesting that EGF enemas are an effective treatment for active left-sided ulcerative colitis A multicentre double-blind study was conducted to evaluate the efficacy and tolerability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis ( less than 20 cm ) . The study end point was the determination of clinical , endoscopic , and histologic remission rates at 4 weeks . Eleven patients , nine receiving placebo  and two receiving 1.5 g mesalazine , withdrew during trial , mostly because of worsening of symptoms . At 4 weeks clinical remission was achieved in 7 of 31 ( 39 % ) patients with placebo , in 22 of 32 ( 69 % ) patients in the 1 g mesalazine group , and 23 of 31 ( 74 % ) patients in the 1.5 g mesalazine group . No serious clinical or biochemical side effect of treatment was reported . Mesalazine suppositories are safe , well tolerated , and very effective in patients with active distal proctosigmoiditis : 500 mg twice daily appears a suitable dose regimen Forty-five of 47 patients with distal ulcerative colitis completed a two-week double-blind , r and omized , controlled trial to determine if 4-aminosalicylic acid ( 4-ASA ) enemas , 1 g bid or 2 g bid , were therapeutically effective compared to placebo .  Forty-one patients enrolled because they were refractory to or had side effects during conventional therapy with sulfasalazine or corticosteroids .  Proctoscopic examination was done before and after two weeks of treatment . Patients kept daily diaries assessing : ( 1 ) blood in stools , ( 2 ) mucus in stools , ( 3 ) tenesmus , ( 4 ) abdominal pain , ( 5 ) loss of appetite , ( 6 ) fatigue , ( 7 ) weight loss , and ( 8) malaise . Severity of each symptom ranged from 0 ( absent ) to 3 ( severe ) . A total severity score was calculated from the above for each patient . At the end of the two-week study , 35 patients elected to take 4-ASA  in an open-label trial for one year . 4-ASA enemas in the 1-g bid but not the 2-g bid dosage were significantly more effective in improving symptoms than placebo : P<-0.05 . Neither dose of 4-ASA enema was better than placebo in improving the sigmoidoscopic appearance at the end of two-weeks . Forty-six percent of patients had complete resolution of all signs and symptoms in the open-label trial and 31 % were better but still had sigmoidoscopic evidence of disease , a total response rate of 77 % . Side effects were similar in the placebo and 4-ASA groups . We conclude that 4-ASA enemas in a dose of 1 g bid are safe and effective in the treatment of distal ulcerative colitis BACKGROUND Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis . AIM To assess , in a multicenter , r and omized , double-blind study , the tolerability and safety of topical beclomethasone diproprionate ( 3 mg ) enema and foam versus mesalazine ( 2 g ) enema and foam in mild-moderate distal ulcerative colitis . PATIENTS In 15 referral gastrointestinal units , 99 patients with distal ulcerative colitis were enrolled . This number was lower than planned according to the statistical analysis , due to a low recruitment rate . METHODS Patients were r and omly assigned to r and om preparations ( beclomethasone diproprionate enema , beclomethasone diproprionate foam , mesalazine enema , mesalazine foam ) once nightly for 8 weeks , with clinical and endoscopical assessment ( Disease Activity Index score ) at baseline ( T0 ) , 4 ( T4 ) and 8 weeks ( T8 ) . Results were expressed as median and range ( 95 % confidence interval ) . The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student 's t-test or the Wilcoxon-Mann-Whitney test . RESULTS Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 ( response at T4 : beclomethasone diproprionate 78 % [ 95 % confidence interval 0.6 - 0.8 ] versus mesalazine 79 % [ 95 % confidence interval 0.6 - 0.8 ] ; T8 : beclomethasone diproprionate 84 % [ 95 % confidence interval 0.7 - 0.9 ] versus mesalazine 90 % [ 95 % confidence interval 0.7 - 1.0 ] ; p = n.s . ; remission at T4 : beclomethasone diproprionate 24 % [ 95 % confidence interval 0.1 - 0.3 ] versus mesalazine 28 % [ 95 % confidence interval 0.1 - 0.3 ] ; remission at T8 : beclomethasone diproprionate 36 % [ 95 % confidence interval 0.2 - 0.5 ] versus mesalazine 52 % [ 95 % confidence interval 0.3 - 0.6 ] ; p = n.s . ) . The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups ( T4 versus T0 : beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p<0.0001 ; beclomethasone diproprionate enema 4 versus 6 , mesalazine enema 3 versus 6 , mesalazine foam 3.5 versus 7 , p<0.001 for all three groups ; T8 versus T0 : p<0.01 ) . The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam ( Disease Activity Index : 2 versus 4 and 1 versus 4 , respectively ; p<0.05 ) and in the mesalazine enema ( Disease Activity Index : 1.5 , range 0 - 4 versus 3 , range 0 - 12 ; p<0.01 ) , but not in the mesalazine foam group ( Disease Activity Index : 1 , range 0 - 9 versus 3.5 , range 0 - 8 ; p = n.s . ) . The safety profile was favourable for all groups . CONCLUSIONS Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis OBJECTIVE : There are few estimates of the incidence and prevalence of inflammatory bowel disease in North American communities . We sought to estimate the incidence and prevalence of inflammatory bowel disease ( IBD ) , including Crohn 's disease ( CD ) , and ulcerative colitis ( UC ) , among 3.2 million members of Kaiser Permanente , Northern California , for the period 1996–2002 . METHODS : All health plan members who had one or more diagnoses of CD ( ICD-9 code 555 ) or UC ( ICD-9 code 556 ) on computerized records during the period 1996–2002 and with at least 12 months of membership were identified as possible IBD cases ( N = 12,059 ) . We r and omly sample d 24 % of these for chart review to confirm the diagnosis and obtain the initial diagnosis date . Incidence rates and the point prevalence on December 31 , 2002 were st and ardized to the 2000 U. S. Census . RESULTS : The annual incidence rate per 100,000 persons was 6.3 for CD ( 95 % confidence interval [ CI ] , 5.6–7.0 ) and 12.0 for UC ( CI , 11.0–13.0 ) . The point prevalence per 100,000 on December 31 , 2002 was 96.3 for CD ( 95 % CI , 89.6–103.0 ) and 155.8 for UC ( 95 % CI , 146.6–164.9 ) , increasing to 100.3 and 205.8 per 100,000 , respectively , when hospital discharge data from 1985 to 1995 were included . The age-specific incidence of CD was bimodal , while UC incidence rose in early adulthood and remained elevated with advancing age . CONCLUSIONS : The incidence we estimated for CD was similar to the previous U. S. estimate . Our incidence estimate for UC was much higher than the previous U.S. estimate , but similar to that of recent Canadian and European studies . The prevalence we estimated for CD was somewhat lower than previous estimates Background : Tacrolimus is a potent immunomodulator that is effective in the systemic treatment of inflammatory bowel diseases ( IBD ) . However , potential toxicity and systemic ( side ) effects after oral intake limit its use . We investigated the local applicability and safety of tacrolimus for distal colitis . Methods : Patients with refractory left‐sided colitis or proctitis were treated for 4 weeks with a daily tacrolimus 2–4 mg enema or 2 mg suppository .  Safety of local tacrolimus treatment was assessed by measurement of whole blood tacrolimus trough levels by monitoring liver and kidney function and blood glucose levels . Efficacy of treatment was assessed by comparing the disease activity index ( DAI ) in ulcerative colitis ( UC ) patients and endoscopic and histologic appearances before and after 4 weeks of treatment . Results : Nineteen patients with left‐sided colitis ( n = 7 ) or proctitis ( n = 12 ) were treated . Two patients with left‐sided colitis had Crohn 's disease ( CD ) , the other 17 patients had UC . None of the patients developed side effects . Blood trough levels of tacrolimus  were too low to induce systemic immune suppression . Thirteen of 19 patients ( 3/5 left‐sided UC , 0/2 left‐sided CD , and 10/12 proctitis ) showed clinical improvement of disease activity after 4 weeks of local tacrolimus treatment . Moreover , a significant improvement of histological appearance was observed in the suppository‐treated group . Conclusions : This study demonstrates that local colonic application of tacrolimus 2–4 mg daily in patients with refractory distal colitis is feasible , probably safe , and potentially efficacious , and therefore opens the need for a further , r and omized trial Twenty-five patients with active left-sided ulcerative colitis were r and omly assigned to receive either 2 g of 4-aminosalicylic acid ( para-aminosalicylic acid ) or placebo in a 60-mL volume as a nightly retention enema . The duration of treatment was 8 weeks . Disease activity was assessed by grading clinical symptoms of blood , mucus , urgency , sigmoidoscopic findings , and degree of histologic inflammation in rectal biopsies . At 8 weeks , 10 of 12 patients ( 83 % ; 95 % confidence interval [ CI ] , 55 % to 97 % ) who received 4-aminosalicylic acid showed improvement in clinical , sigmoidoscopic , and histologic variables . In contrast , only 2 of 13 patients ( 15 % , 95 % CI , 4 % to 38 % ) who had received placebo showed clinical improvement ( P less than 0.005 ) . The 11 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid enemas . Of the 11 , 9 showed clinical , sigmoidoscopic , and histologic improvement . No adverse effects were seen . 4-Aminosalicylic acid enemas are a safe and effective means of treating left-sided ulcerative colitis Alicaforsen is an antisense oligonucleotide design ed to inhibit expression of human intercellular adhesion molecule 1 . Previous clinical studies have demonstrated activity of alicaforsen enema in ulcerative colitis and pouchitis 5-Aminosalicylic acid ( 5-ASA ) , the active moiety of sulphasalazine ( SASP ) , was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage . A double blind study was carried out using enemas containing 1 , 2 , or 4 g or 5-ASA or placebo for a one month treatment period . One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate .  Clinical , sigmoidoscopic , and histological assessment s were carried out at the beginning of the study and after 15 and 30 days of treatment . All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema ( p less than 0.001 ) but no difference was detected among the patients receiving differing concentrations of 5-ASA . This study suggests that 1 g 5-ASA ( in a 100 ml enema ) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis Oral and topical mesalazine formulations are effective in active ulcerative colitis , but little is known on the efficacy of combined treatment The aim of this study was to evaluate whether budesonide enema ( 2 mg/100 ml ) had a significantly better effect than placebo in the treatment of distal ulcerative colitis or proctitis . The trial was of controlled , r and omized , double-blind design and included 41 treated patients . The treatment time was 4 weeks , with revisits after 2 and 4 weeks . If no improvement was seen , the patient could be switched over to open-label therapy with budesonide enema .  Sigmoidoscopy , histology , blood chemistry , and diary cards were used for estimating the effect of treatment . The results showed that budesonide was superior to placebo .  Sigmoidoscopy and biopsy scores improved significantly ( p less than 0.01 ) in budesonide-treated patients compared with placebo . Significantly more patients switched over to open budesonide treatment in the placebo group owing to lack of efficacy compared with budesonide ( p less than 0.001 ) . No drug-related adverse experiences occurred , and there was no decrease in endogenous morning plasma cortisol levels . It is concluded that budesonide enema appears to be an effective and safe treatment for distal ulcerative colitis and proctitis Pharmacokinetic data obtained after one dose of a 2‐mg budesonide enema were compared with data obtained after the last dose of four weeks of daily treatment in 24 patients with active distal ulcerative colitis or proctitis . This open multicentre study involved 28 eligible patients . Sigmoidoscopy and biopsy scores improved significantly ( P < 0.002 ) during the four‐week treatment period . Maximal plasma concentration ( Cmax )  of budesonide was 2.1 nmol/L 1.3 h after the first dose and 2.5 nmol/L 1.2 h after the last dose ; the difference was not significant . The area under the curve ( AUC ) of plasma concentration vs. time was after the first dose 9.7 nmol h/L and after the last dose 11.6 nmol h/L ( P < 0.03 ) . The small increase in AUC may be attributed to improved absorption . During the last dose interval , minimal plasma concentration was below the limit of quantitation in most subjects . The Cmax and AUC of budesonide  increased slightly after four weeks of treatment , but budesonide  did not accumulate . Mean morning plasma cortisol values did not change significantly during treatment ( P= 0.083 ) , although a small change in cortisol levels between the first visit ( pre‐treatment ) and last visit was positively correlated to the C. of budesonide measured at the last visit ( P= 0.012 ) Thirty‐seven patients suffering an attack of acute distal ulcerative colitis of mild or moderate severity were r and omized in a double‐blind , doubledummy fashion to receive either 800 mg oral mesalazine four times daily ( 18 patients ) or steroid enemas twice daily ( 19 patients ) for 4 weeks . Both treatments were well tolerated with no adverse effects . Three patients in each group were withdrawn because of clinical deterioration but both treatments produced significant clinical improvement with decreases in stool frequency and scores for urgency , bleeding and tenesmus . There were no significant differences between the treatments although there was a slight trend in favour of the enemas for reduction in rectal bleeding . Activity of the colitis as grade d at sigmoidoscopy also decreased significantly with both treatments and there were corresponding improvements in histological parameters of inflammatory activity assessed with the aid of a computerized morphometric system . Little correlation was seen between clinical , sigmoidoscopic and histological changes Background : Mesalamine suppositories are first‐line therapy in active ulcerative proctitis ; the st and ard regime still recommends multiple doses per day . The primary objective of this study was to show the noninferiority of once‐daily administration of a novel 1 g mesalamine suppository versus thrice‐daily administration of the 0.5 g mesalamine suppository . Methods : This was a single‐blind ( investigator‐blinded ) , r and omized , multicenter , comparative , Phase III clinical trial . Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6‐week period . The primary endpoint was rate of remission ( Disease Activity Index below 4 ) . Results : In all , 354 patients were evaluable for safety and per‐ protocol analysis . The new regimen demonstrated noninferiority : The percentage of patients with remission was 87.9 % for the once‐daily 1 g mesalamine suppository and 90.7 % for the thrice‐daily 0.5 g mesalamine suppository . Each regimen result ed in prompt cessation of clinical symptoms ( e.g. , median time to ≤3 stools per day ( all without blood ) : 5 days in the 1 g mesalamine once‐daily and 7 days in the 0.5 g mesalamine thrice‐daily group ) . Patients preferred applying suppositories once a day . Conclusions : In active ulcerative proctitis the once‐daily administration of a 1 g mesalamine suppository is as effective and safe , yet considerably more convenient , than the st and ard thrice‐daily administration of a 0.5 g mesalamine suppository . ( Inflamm Bowel Dis 2010 The efficacy of 5-aminosalicylic acid enemas in maintaining remission in left-sided ulcerative colitis was studied . Twenty-five patients in remission for at least 2 mo were r and omized to receive either 1-g 5-aminosalicylic acid or placebo enemas daily and were followed up for 1 yr . Eleven of 13 patients r and omized to placebo  relapsed after a mean of 16 wk . Nine of 12 patients r and omized to 5-aminosalicylic acid remained in remission for 1 yr , 2 others in remission withdrew by request , and 1 relapsed at 10 wk . The difference between relapse rate on 1-g 5-aminosalicylic acid versus placebo was significant ( p less than 0.005 ) . Seven patients entered the blinded trial a second time . Three of 4 patients r and omized to 5-aminosalicylic acid  remained in remission and 1 relapsed . Three r and omized to placebo  relapsed at a mean of 14 wk . One-gram 5-aminosalicylic acid enemas are safe and effective in maintaining remission in patients with left-sided ulcerative colitis Goals : Therapy for active ulcerative colitis ( UC ) usually involves rectal formulations of corticosteroids ( CS ) , which are characterized by the risk of systemic steroid-related adverse effects . Background : To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate ( BDP ) versus mesalamine ( 5-ASA ) in the treatment of active UC . Study : Patients with mild to moderate distal active UC were r and omized to a 6-week treatment with BDP 3 mg enema o.d . or 5-ASA 1 g enema daily in a single-blind , multicenter , parallel-group , controlled study . The primary efficacy variable was the decrease in Disease Activity Index ( DAI ) score . Safety variables were adrenal function , monitoring of adverse events , vital signs , and laboratory parameters . Results : A total of 217 patients were enrolled and treated with BDP ( n = 111 ) or 5-ASA ( n = 106 ) . A significant decrease in the DAI score ( P < 0.05 ) was observed in both treatment groups , with a clinical remission rate of 36.7 % in the BDP group and of 29.2 % in the 5-ASA group . Both treatments were well tolerated . No changes from baseline in morning cortisol levels were observed in the BDP group . Conclusions : BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC , without interference with pituitary adrenal axis Abstract INTRODUCTION : Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema . Foam offers patients better tolerability than an enema . In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam . METHODS : Two hundred fifty-one patients with proctosigmoiditis were r and omly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks . RESULTS : Remission rates were comparable in the budesonide and hydrocortisone groups , 53 and 52 percent , respectively . The mean disease activity index for the two groups decreased to a similar extent , from 7.2 ± 1.9 and 7 ± 2 to 3.6 ± 3.1 and 3.9 ± 3.4 in the budesonide and hydrocortisone groups , respectively . In a subgroup of patients who had not responded to rectal administration of mesalamine , 23 of 44 ( 52 percent ) patients who received budesonide responded favorably to the foam , as compared with 14 of 38 ( 37 percent ) patients who received hydrocortisone ( P = not significant ) . Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients . CONCLUSIONS : This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis Enemas of 4-amino-salicylic acid ( 4-ASA ) have been compared with placebo enemas in a double-blind study for the treatment of distal ulcerative colitis of mild to moderate severity . 30 patients were r and omised to receive enemas containing 1 g of 4-ASA or placebo , and 22 to receive 2-gram enemas of 4-ASA or placebo .  For each dose of 4-ASA there was clinical and sigmoidoscopic improvement , which reached significance when all patients receiving 4-ASA enemas were compared with those receiving placebo enemas ( Cochran 's test : p less than 0.005 ) . There was also a trend towards histological improvement , but this failed to reach the level of significance . These findings suggest that 4-ASA may provide a stable , inexpensive alternative to 5-ASA for the topical treatment of ulcerative colitis or for linking to carrier molecules for release in the colon Objective : To evaluate the safety and efficacy of an enema formulation of alicaforsen , an antisense inhibitor of intercellular adhesion molecule , after 1 , 3 , and 6 months . Methods : This was a r and omised , placebo controlled , double blind , escalating dose multicentre study in 40 patients with mild to moderately active distal ulcerative colitis ( disease activity index ( DAI ) 4–10 ) . Patients were assigned to four dosing cohorts of 10 patients each ( eight active , two placebo ) . Each patient received 60 ml of alicaforsen enema ( 0.1 , 0.5 , 2 , or 4 mg/ml or placebo ) once daily for 28 consecutive days . Safety and efficacy ( DAI and clinical activity index ) scores were evaluated up to six months after initiation of dosing . Results : At day 29 , alicaforsen enema result ed in dose dependent improvement in DAI ( overall p = 0.003 ) . Alicaforsen 4 mg/ml improved DAI by 70 % compared with the placebo response of 28 % ( p = 0.004 ) . Alicaforsen 2 and 4 mg/ml improved DAI status by 72 % and 68 % compared with a placebo response of 11.5 % at month 3 ( p = 0.016 and 0.021 , respectively ) . Specifically , DAI improved from 5.6 to 1.6 and from 6.3 to 2.5 in the 2 and 4 mg/ml groups compared with placebo ( 7.5 to 6.1 ) . None of the patients in the 4 mg/ml group compared with 4/8 placebo patients required additional medical or surgical intervention over baseline during the six month period after starting the enema treatment . The safety profile was favourable . Conclusions : Alicaforsen enema showed promising acute and long term benefit in patients with mild to moderate descending ulcerative colitis .  Alicaforsen enemas had a favourable safety profile . These findings require verification in larger r and omised controlled clinical trials
BACKGROUND Many therapeutic options are available for patients with distal forms of ulcerative colitis ( UC ) .
Rectal therapies ( e.g. , suppositories , foams , gels , and enemas ) may be recommended either alone or in combination with oral treatment .
Compared with oral therapies , rectal therapies are underused in patients with distal forms of UC , although rectal therapies have favorable efficacy and safety profiles .