Budesonide in the treatment of inflammatory bowel disease: The first year of experience in clinical practice Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group. Oral budesonide therapy for steroid‐dependent ulcerative colitis: a pilot trial Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion. Evaluation of oral budesonide in the treatment of active distal ulcerative colitis. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study 3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial. Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee The outcome of childhood Haemophilus influenzae meningitis. A population based study. Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis. Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. Budesonide Foam vs. Hydrocortisone Acetate Foam in the Treatment of Active Ulcerative Proctosigmoiditis
Background : Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn 's disease involving the ileum and ascending colon . Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission , with less frequent steroid side effects than conventional steroids . We sought to determine the benefit of this medication in clinical practice and to identify any non‐ FDA ‐approved uses that may warrant further study . Methods : Patients in whom oral budesonide was prescribed between November 1 , 2001 and October 31 , 2002 , were identified and medical records were review ed . Patients were categorized by indication for therapy : ileocolonic Crohn 's disease ( group 1 ) , Crohn 's disease elsewhere ( group 2 ) , and other conditions ( group 3 ) . Results : A total of 225 patients were identified ( 108 in group 1 , 62 in group 2 , and 55 in group 3 ) . Group 3 included patients with microscopic colitis ( n = 28 ) , pouchitis ( n = 13 ) , ulcerative colitis ( n = 12 ) , and celiac disease ( n = 2 ) . A favorable outcome occurred in 61 % of group 1 patients but only 24 % of patients in group 2 . In group 3 , only microscopic colitis patients and pouchitis patients experienced response rates > 50 % ( 77 % and 60 % , respectively ) . Conclusion : Budesonide is effective in a majority of patients with ileocolonic Crohn 's disease and microscopic colitis , which is consistent with results reported from clinical trials . A majority of patients with pouchitis also benefit from budesonide therapy , but prospect i ve controlled trials are necessary to clarify the benefit in this group OBJECTIVE --To assess the safety and efficacy of a preparation of mesalazine ( 5-aminosalicylic acid ) coated with a pH dependent resin ( Eudragit L ) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis . DESIGN --Eight week r and omised double blind parallel group study . SETTING --Forty six gastroenterology outpatient clinics in seven countries . PATIENTS --Two hundred and twenty patients aged 18 - 70 who met the following criteria : clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4 ; no concomitant treatment for ulcerative colitis ; no hypersensitivity to salicylates or sulphonamides . Of the 164 patients eligible for efficacy analysis , 87 received the coated preparation of mesalazine and 77 sulphasalazine . Most of the remaining patients ( 28 in each group ) were ineligible for the efficacy analysis because of treatment with steroid enemas . All pretrial characteristics were comparable in the two treatment groups . INTERVENTIONS --Coated mesalazine ( Mesasal ) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks . Compliance monitored by pill counts . END POINT-- Clinical and endoscopic remission . MEASUREMENTS AND MAIN RESULTS -- Clinical activity measured by daily diary cards , assessment by investigators , and laboratory findings . Endoscopic evaluation at week 8 . After four weeks 50 of 70 patients ( 71 % ) taking coated mesalazine and 38 of 58 ( 66 % ) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74 % ( 37/50 patients ) and 81 % ( 35/43 ) in the two treatment groups respectively . Endoscopic remission at eight weeks was recorded in 20 of 41 patients ( 49 % ) taking coated mesalazine and 18 of 38 ( 47 % ) taking sulphasalazine . There was a higher incidence of adverse events among patients taking sulphasalazine ( 25/105 ; 24 % ) than among those taking coated mesalazine ( 16/115 ; 14 % ) . CONCLUSION --Mesalazine coated with Eudragit L is a safe , logical alternative to sulphasalazine 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 Forty mg has been shown to be the optimal daily dosage of prednisone for out patients requiring oral steroids for active proctocolitis . Although daily doses of oral steroids are commonly divided , a single dose each morning causes less adrenal suppression and is more convenient to take . A r and omized controlled trial has been performed on patients with proctocolitis , in which 23 received 40 mg prednisolone each morning as one dose , and 22 received 10 mg four times a day  , over two weeks  . Physicians unaware of the dosage schedule scored the disease activity and assessed the steroid side-effects when the patient entered the trial , at day 7 and at day 14 . Of those taking the divided dose the disease improved in 17 and failed to improve in five . No side-effects were observed in ten patients . Of those receiving a once daily regimen , 17 improved and six did not . Nine patients had no side-effects . Further assessment showed no difference between the two groups either in response rate or side-effects produced . When oral steroids are indicated for active proctocolitis , 40 mg prednisolone , as a single dose each morning can be recommended BACKGROUND Crohn 's disease is often treated with glucocorticoids or mesalamine . We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn 's disease affecting the ileum , the ascending colon , or both . METHODS In a double-blind , multicenter trial , we enrolled 182 patients with scores of 200 to 400 on the Crohn 's Disease Activity Index ( with higher scores indicating greater disease activity ) and r and omly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks . The primary efficacy variable was clinical remission , defined as a score of 150 or less on the Crohn 's Disease Activity Index . RESULTS In the analysis of all patients who received at least one dose of study drug , the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group ( P=0.001 ) ; the respective rates after 16 weeks of treatment were 62 percent and 36 percent ( P<0.001 ) . Seventy-seven patients in the budesonide group completed the 16 weeks of treatment , as compared with 50 patients in the mesalamine group ( P<0.001 ) . The numbers of patients with adverse events were similar in the two groups , but those assigned to budesonide had fewer severe adverse events . Among patients who completed 16 weeks of treatment , the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients ( P=0.06 ) ; 90 percent and 100 percent , respectively , had normal increases in cortisol in response to cosyntropin ( P=0.02 ) . CONCLUSIONS In patients with active Crohn 's disease affecting the ileum , the ascending colon , or both , a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine Budesonide , a corticosteroid with high topical anti‐inflammatory activity and low systemic activity , has been shown to prolong time to relapse in Crohn 's disease . In the present study , the efficacy of budesonide in an oral pH‐modified‐release formulation was evaluated for maintenance treatment in patients with steroid‐dependent ulcerative colitis Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease . The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation . We now report a prospect i ve study comparing 111In-granulocyte scanning with endoscopy , histology , and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease . In 52 patients with Crohn 's disease or ulcerative colitis , disease extent and severity were assessed macroscopically , histologically , or by scanning using a numerical grading system . Excellent correlations were found between both endoscopy and histology and 111In scans [ r = 0.90 ( endoscopy ) and r = 0.90 ( histology ) for extent ; r = 0.86 and r = 0.91 for disease activity ] . Severity grade d by scanning also showed a close correlation with fecal 111In-granulocyte excretion ( r = 0.90 ) . Indium 111-granulocyte scans are a rapid , accurate , noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease Budesonide , a topical corticosteroid , has proven useful for the management of Crohn 's disease . Its efficacy is similar to prednisone but it has fewer side effects . A new pH-modified release capsule ( Budenofalk ) is probably efficacious in distal ulcerative colitis . The aim of the present study was to establish the pharmacokinetics , pharmacodynamics , and safety of two dosage regimens of budesonide capsules and to obtain efficacy information . Budenofalk 9 mg daily was administered as a single dose 9 mg in 8 patients and as three 3 mg doses in 7 patients with active distal ulcerative colitis for 8 weeks . Symptoms were assessed at three timepoints during the study : baseline , 4 and 8 weeks after start of treatment . Endoscopic evaluation and budesonide concentration in mucosal biopsy specimens was performed at 0 and 8 weeks . A pharmacokinetic profile and pharmacodynamic profile ( cortisol , lymphocytes and neutrophils ) was performed at day 5 . In the 9 mg o.d . group , higher peak concentrations and systemic availability was found compared to the 3 mg t.i.d . group . Cortisol suppression was more pronounced after 9 mg o.d . than after 3 mg t.i.d . Lag-time , AUC and pharmacodynamic effects were comparable ( 14 % mean decrease lymphocyte count and 26 % mean increase neutrophil count ) . Mucosal biopsy specimens in the distal colon revealed significant budesonide levels with both regimens . After 8 weeks , 71 % in the 9 mg o.d . group and 38 % in the 3 t.i.d . group responded . The endoscopic index improved from 10 + /- 2 to 2 + /- 3 ( p < 0.001 ) with 9 mg o.d . and from 9 + /- 2 to 4 + /- 4.7 ( p = 0.02 ) with 3 mg t.i.d . The pharmacokinetic and pharmacodynamic profiles found in this study indicate that Budenofalk reaches the distal part of colon and rectum , but further studies to vali date the budesonide assay in the mucosa and comparison with a control group are necessary . This limited study suggests that Budenofalk is effective in distal colitis and side effects are rare . Based on these observations a large clinical trial using 9 mg o.d . is indicated to confirm efficacy and assess further possible side effects Objective Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System ( MMX ) technology to extend release to the colon . This study compared the efficacy of budesonide MMX with placebo in patients with active , mild-to-moderate ulcerative colitis ( UC ) . Design Patients were r and omised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg , or Entocort EC 9 mg ( budesonide controlled ileal-release capsules ; reference arm ) or placebo once daily for 8 weeks . The primary endpoint was combined clinical and endoscopic remission , defined as UC Disease Activity Index score ≤1 with a score of 0 for rectal bleeding and stool frequency , no mucosal friability on colonoscopy , and a ≥1-point reduction in endoscopic index score from baseline . Results 410 patients were evaluated for efficacy . Combined clinical and endoscopic remission rates  with budesonide MMX 9 mg or 6 mg , Entocort EC and placebo were 17.4 % , 8.3 % , 12.6 % and 4.5 % , respectively . The difference between budesonide MMX 9 mg and placebo was significant ( OR 4.49 ; 95 % CI 1.47 to 13.72 ; p=0.0047 ) . Budesonide MMX 9 mg was associated with numerically higher rates of clinical ( 42.2 % vs 33.7 % ) and endoscopic improvement ( 42.2 % vs 31.5 % ) versus  placebo . The rate of histological healing ( 16.5 % vs 6.7 % ; p=0.0361 ) and proportion of patients with symptom resolution ( 23.9 % vs 11.2 % ; p=0.0220 ) were significantly higher for budesonide MMX 9 mg than  placebo . Adverse event profiles were similar across groups . Conclusion Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active , mild-to-moderate UC BACKGROUND AND AIMS Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis ( UC ) . This study aim ed to demonstrate non-inferiority for oral 9 mg budesonide once daily ( OD ) versus 3 g mesalazine granules OD . METHODS This was an eight-week r and omised , double-blind , double-dummy , multicentre study in which patients with mild-to-moderately active UC , defined as Clinical Activity Index ( CAI ) ≥6 and Endoscopic Index ( EI ) ≥4 , received budesonide ( Budenofalk ® 3 mg capsules × 3 ) or mesalazine ( Salofalk ® 1000 mg granules × 3 ) . The primary endpoint was clinical remission at week 8 ( CAI ≤4 with stool frequency and rectal bleeding subscores of " 0 " ) . RESULTS 343 patients were r and omised ( 177 budesonide , 166 mesalazine ) . Fewer patients achieved the primary endpoint with budesonide versus mesalazine ( 70/177 [ 39.5 % ] versus 91/166 [ 54.8 % ] ) with a difference in proportions of -15.3 % ( 95 % CI [ -25.7 % , -4.8 % ] ; p=0.520 for non-inferiority ) . The median time to first resolution of symptoms was 14.0 days ( budesonide ) and 11.0 days ( mesalazine ) ( hazard ratio 1.19 ; 95 % CI [ 0.94 , 1.51 ] ) . Mucosal healing was observed in 54/177 ( 30.5 % ) budesonide patients versus 65/166 ( 39.2 % ) mesalazine patients , a difference of -8.6 % ( 95 % CI [ -18.7 % , 1.4 % ] ; p=0.093 ) . The incidences of adverse events  ( budesonide 26.6 % , mesalazine 25.3 % ) and serious adverse events ( budesonide 1.7 % , mesalazine 1.2 % ) were similar . CONCLUSIONS Once-daily 3 g mesalazine administered as granules is superior to 9 mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC . However , it is noteworthy that remission of UC was attained in about 40 % of budesonide-treated patients with a rapid onset of resolution 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 OBJECTIVE To determine the morbidity and mortality from childhood Haemophilus influenzae type b ( Hib ) meningitis in a well defined population . DESIGN Retrospective survey 1985 - 1987 and prospect i ve surveillance of hospital laboratories 1989 - 1990 . Information on outcome of meningitis was obtained from hospital records and attending physicians and , in 1989 - 1990 , from a survey of the children 's parents . SETTING Sydney Statistical Division , which had a population of children aged 0 - 4 years of 229,165 in 1986 and 263,758 in 1990 . PATIENTS Eligible children were aged from one month to four years and had clinical and microbiological evidence of Hib meningitis on st and ard criteria . RESULTS There were 229 eligible children . Twelve were excluded ( seven died and five had pre-existing neurological deficits ) . A neurological deficit was detected at the time of hospital discharge in 45 patients ( 21 % ) and persisted for 12 months or longer in 29 patients ( 13 % ) . Follow-up information was available for 165 ( 96 % ) children who were normal at the time of hospital discharge and persistent deficits were recorded in 12 ( 7 % ) of these children . Forty-one children ( 19 % ) had readily recognisable neurological or hearing problems : nine ( 4 % ) had persistent severe neurological deficits and seven ( 3 % ) had severe hearing loss requiring hearing aids or a cochlear implant . Age had a significant influence on outcome . The youngest children were significantly more likely to be admitted to intensive care . Severe neurological deficits showed a significant negative trend with increasing age ( P = 0.03 ) . Severe unilateral or bilateral sensorineural loss ( odds ratio [ OR ] 8.0 , 95 % confidence interval [ CI ] 1.5 - 81 ) and ataxia at discharge ( OR 13.3 , 95 % CI 2.8 - 128 ) were noticeably more common in children over two years of age , with a significant positive trend ( P < or = 0.001 ) with increasing age . Patients requiring intensive care were much more likely to have an adverse outcome , particularly if positive pressure ventilation was needed . CONCLUSIONS These data provide population -based estimates of the minimum incidence of adverse outcomes from Hib meningitis in an urban community with good access to medical services . This is important in assessing the impact of Hib vaccination , as meningitis is responsible for most of the long-term morbidity from childhood invasive Hib disease . Determination of the relationship between morbidity and age is important for assessing alternative vaccine strategies BACKGROUND & AIMS Systemic glucocorticosteroids ( GCSs ) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects . Therefore , new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition . The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided , mild to moderately active ulcerative colitis . METHODS A 9-week , r and omized , double-blind , controlled trial was performed , and treatments with 10 mg budesonide or 40 mg prednisolone daily , both gradually tapered , were compared . Endoscopic improvement and effect on endogenous plasma cortisol were assessed . RESULTS Thirty-four patients were administered budesonide , and 38 patients were administered prednisolone .  Mean endoscopic scores improved significantly in both groups but without difference between the groups . Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study . Morning plasma cortisol levels were suppressed in the prednisolone group ( entry , 449 nmol/L ; 2 weeks , 116 nmol/L ; 4 weeks , 195 nmol/L ) but were unchanged in the budesonide group . CONCLUSIONS The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels . This concept merits further evaluation BACKGROUND & AIMS Budesonide is a corticosteroid with minimal systemic corticosteroid activity due to first-pass hepatic metabolism . Budesonide MMX ® is a once-daily oral formulation of budesonide that extends budesonide release throughout the colon using multi-matrix system ( MMX ) technology . METHODS We performed a r and omized , double-blind , double-dummy , placebo-controlled trial to evaluate the efficacy of budesonide MMX for induction of remission in 509 patients with active , mild to moderate ulcerative colitis ( UC ) . Patients were r and omly assigned to groups that were given budesonide MMX ( 9 mg or 6 mg ) , mesalamine ( 2.4 g , as reference ) , or placebo for 8 weeks . The primary end point was remission at week 8 . RESULTS The rates of remission at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 17.9 % , 13.2 % , and 12.1 % , respectively , compared with 7.4 % for placebo ( P = .0143 , P = .1393 , and P = .2200 ) . The rates of clinical improvement at week 8 among patients given 9 mg or 6 mg budesonide MMX or mesalamine were 33.3 % , 30.6 % , and 33.9 % , respectively , compared with 24.8 % for placebo ( P = .1420 , P = .3146 , and P = .1189 ) . The rates of endoscopic improvement at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 41.5 % , 35.5 % , and 33.1 % , respectively , compared with 33.1 % for placebo . The rates of symptom resolution at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 28.5 % , 28.9 % , and 25.0 % , respectively , compared with 16.5 % for placebo ( P = .0258 , P = .0214 , and P = .1025 ) . Adverse events occurred at similar frequencies among groups . CONCLUSIONS Budesonide MMX ( 9 mg ) was safe and more effective than placebo in inducing remission in patients with active , mild to moderate UC 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 We assessed oral 5-aminosalicylic acid ( 5-ASA ) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind , placebo-controlled trial . Patients were r and omly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks . The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians ' assessment s at three-week intervals and by patients ' recordings of daily symptoms . Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo ( P less than 0.0001 , rank-sum test ) . At a dosage of 1.6 g per day , the response was twice as good as with placebo , but the difference did not reach statistical significance ( P = 0.51 ) . Age , sex , duration of disease , duration of active symptoms , or extent of disease did not affect the clinical outcome . We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy , at least in the short term , for mildly to moderately active ulcerative colitis The efficacy of a capsule formulation of mesalamine was assessed in 374 patients with mild to moderately active ulcerative colitis . Patients , stratified to pancolitis or left-sided disease , received either placebo or mesalamine at 1 , 2 , or 4 g daily for 8 wk . Efficacy was assessed using clinical improvement -- physician global assessment , sigmoidoscopic index , biopsy score , trips to the toilet , and clinical symptoms ( abdominal pain , urgency , stool consistency , and rectal bleeding)-- and induction of remission ( more stringent criteria for physician global assessment , sigmoidoscopic index , and biopsy score ) . For physician global assessment of treatment benefit , 79 % and 84 % of patients on the 2-g and 4-g doses of mesalamine , respectively , received treatment benefit , compared with 54 % on placebo ( p < or = 0.0002 ) . For the physician global assessment of treatment success , both the 2-g and 4-g doses of mesalamine were superior to placebo ( 57 % and 59 % of patients , p = 0.0021 and 0.0012 , respectively ) , compared with 36 % on placebo . Both the 2-g and 4-g doses produced statistically significant macroscopic ( endoscopic ) improvement compared with placebo ( p < 0.004 ) . The 4-g dose also produced a statistically significant microscopic ( histologic ) improvement compared to placebo ( p < 0.002 ) . Significant improvement compared to placebo was also observed at 2 g and 4 g for the four clinical symptoms and trips to the toilet ( p < or = 0.003 ) . Oral mesalamine capsules were significantly superior to placebo for inducing remission , with 29 % of patients at 2 g and 29 % at 4 g achieving remission by physician global assessment , compared with 12 % on placebo . Forty-four percent and 48 % of patients receiving 2 g and 4 g of mesalamine , respectively , achieved remission by sigmoidoscopic index ( p < 0.05 ) , compared with 31 % on placebo . Thirty-nine percent of patients at 4 g daily achieved microscopic remission , compared with 23 % on placebo ( p < 0.03 ) . Treatment response was not affected by extent of disease or prior steroid or sulfasalazine therapy . These data suggest that controlled-release mesalamine capsules are a safe and effective monotherapy in doses of 2 - 4 g daily for treating mild to moderately active ulcerative colitis , as well as for inducing remission , regardless of prior oral steroid or sulfasalazine therapy or extent of disease BACKGROUND Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis . METHODS We conducted two integrated r and omized , double-blind , placebo-controlled trials of vedolizumab in patients with active disease . In the trial of induction therapy , 374 patients ( cohort 1 ) received  vedolizumab  ( at a dose of 300 mg ) or placebo intravenously at weeks 0 and 2 , and 521 patients ( cohort 2 ) received open-label  vedolizumab at weeks 0 and 2 , with disease evaluation at week 6 . In the trial of maintenance therapy , patients in either cohort who had a response to vedolizumab at week 6 were r and omly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks . A response was defined as a reduction in the Mayo Clinic score ( range , 0 to 12 , with higher scores indicating more active disease ) of at least 3 points and a decrease of at least 30 % from baseline , with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 . RESULTS Response rates at week 6 were 47.1 % and 25.5 % among patients in the vedolizumab group and placebo group , respectively ( difference with adjustment for stratification factors , 21.7 percentage points ; 95 % confidence interval [ CI ] , 11.6 to 31.7 ; P<0.001 ) . At week 52 , 41.8 % of patients who continued to receive vedolizumab every 8 weeks and 44.8 % of patients who continued to receive vedolizumab every 4 weeks were in clinical remission ( Mayo Clinic score ≤2 and no subscore > 1 ) , as compared with 15.9 % of patients who switched to placebo ( adjusted difference , 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [ 95 % CI , 14.9 to 37.2 ; P<0.001 ] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [ 95 % CI , 17.9 to 40.4 ; P<0.001 ] ) . The frequency of adverse events was similar in the vedolizumab and placebo groups . CONCLUSIONS Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis . ( Funded by Millennium Pharmaceuticals ; GEMINI 1 Clinical Trials.gov number , NCT00783718 . ) 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
BACKGROUND Corticosteroids are first-line therapy for induction of remission in ulcerative colitis .
Although corticosteroids may improve symptoms , they have significant adverse effects .
Steroids which act topically , with less systemic side-effects may be more desirable .
Budesonide is a topically acting corticosteroid with extensive first pass hepatic metabolism .
There are currently three formulations of budesonide : two st and ard formulations including a controlled-ileal release capsule and a pH-dependent capsule both design ed to release the drug in the distal small intestine and right colon ; and the newer Budesonide-MMX ® capsule design ed to release the drug throughout the entire colon .
OBJECTIVES The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in ulcerative colitis .