Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial Crohn's disease, fatigue, and infliximab: is there a role for cytokines in the pathogenesis of fatigue? Application of the multidimensional fatigue inventory (MFI-20) in cancer patients receiving radiotherapy. Self-management education for rehabilitation inpatients suffering from inflammatory bowel disease: a cluster-randomized controlled trial. Fluoxetine for Maintenance of Remission and to Improve Quality of Life in Patients with Crohn’s Disease: a Pilot Randomized Placebo-Controlled Trial A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis. Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI) Infliximab Improves Quality of Life in Patients with Crohn's Disease Ferric Maltol Is Effective in Correcting Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results from a Phase-3 Clinical Trial Program Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long‐term extension data from a Phase 3 study Interferon beta-1a for the maintenance of remission in patients with Crohn's disease: results of a phase II dose-finding study Ferumoxytol versus placebo in iron deficiency anemia: efficacy, safety, and quality of life in patients with gastrointestinal disorders Effect of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™, on Symptoms, Fatigue and Quality of Life in Patients with Ulcerative Colitis in a Randomized Single-Blinded Placebo Controlled Study Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial. Effects of Adalimumab Maintenance Therapy on Health-Related Quality of Life of Patients With Crohn's Disease: Patient-Reported Outcomes of the CHARM Trial Infliximab, azathioprine, or combination therapy for Crohn's disease. Safety and Tolerability of Low-dose Naltrexone Therapy in Children With Moderate to Severe Crohn’s Disease: A Pilot Study INSPIRE study: Does stress management improve the course of inflammatory bowel disease and disease‐specific quality of life in distressed patients with ulcerative colitis or crohn's disease? A randomized controlled trial A stress management programme for Crohn's disease. A randomized, placebo-controlled, phase II study of tetomilast in active ulcerative colitis. Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 study Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Influence of inflammatory bowel disease on different dimensions of quality of life Vedolizumab as induction and maintenance therapy for Crohn's disease. Vedolizumab as induction and maintenance therapy for ulcerative colitis. A randomised controlled trial of high versus low long chain triglyceride whole protein feed in active Crohn's disease Long-term Efficacy of Vedolizumab for Ulcerative Colitis Switch to adalimumab in patients with Crohn's disease controlled by maintenance infliximab: prospective randomised SWITCH trial A randomised, double-blind, sham-controlled study of granulocyte/monocyte apheresis for moderate to severe Crohn's disease Fatigue management in patients with IBD: a randomised controlled trial
Background Endogenous opioid peptides have been shown to play a role in the development and /or perpetuation of inflammation . We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease , and antagonism of the opioid – opioid receptor will lead to reversal of inflammation . Aims A r and omized double-blind placebo-controlled study was design ed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn ’s disease . Methods Forty subjects with active Crohn ’s disease were enrolled in the study . R and omized patients received daily oral administration of 4.5-mg naltrexone or placebo . Providers and patients were masked to treatment assignment . The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn ’s Disease Activity Index score ( CDAI ) . The secondary outcome included mucosal healing based upon colonoscopy appearance and histology . Results Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40 % of placebo-treated patients ( p = 0.009 ) . After 12 weeks , 78 % of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn ’s disease endoscopy index severity score ( CDEIS ) from baseline compared to 28 % response in placebo-treated controls ( p = 0.008 ) , and 33 % achieved remission with a CDEIS score < 6 , whereas only 8 % of those on placebo showed the same change . Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo . Conclusions Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn ’s disease compared to placebo-treated controls . Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn ’s disease AIM To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn 's disease ( CD ) patients . METHODS Fourteen CD patients were blinded for treatment and received placebo at baseline , and infliximab 2 wk later , with a follow-up of 4 wk . Blood sample s were drawn on a regular basis , and question naires on fatigue , depression , quality of life , and clinical disease activity were completed at regular intervals . RESULTS After placebo infusion , fatigue scores decreased within 3 d ( 3.5 points + /- 1.1 , P < or= 0.01 ) , but returned to baseline values 14 d after this infusion . The drop of fatigue scores following infliximab infusion sustained until the end of the study ( 3.8 points + /- 1.4 , P < or= 0.05 ) . Quality of life was increased at the end of the study compared to baseline values ( 138.6 + /- 9.4 vs 179.4 + /- 6.7 ; P < or= 0.005 ) , whereas depression scores were decreased ( 20.4 + /- 9.4 vs 11.3 + /- 2.2 ; P < or= 0.01 ) . No correlation between the severity of fatigue and the level of cytokines was observed . CONCLUSION The reduction of fatigue after infliximab infusion is subjective to a placebo effect . The effect of infliximab on fatigue , however , persists while the placebo effect disappears after a short period of time . A clear role of cytokines could not be substantiated In this paper the psychometric properties of the multidimensional fatigue inventory ( MFI-20 ) are established further in cancer patients . The MFI is a 20-item self-report instrument design ed to measure fatigue . It covers the following dimensions : general fatigue , physical fatigue , reduced activity , reduced motivation and mental fatigue . The instrument was used in a Dutch and Scottish sample of cancer patients receiving radiotherapy .  The dimensional structure was assessed using confirmatory factor analyses ( Lisrel 's unweighted least-squares method ) . The hypothesised five-factor model appeared to fit the data in both sample s ( adjusted goodness of fit ; AGFI : 0.97 and 0.98 ) . Internal consistency of the separate scales was good in both the Dutch and Scottish sample s with Cronbach 's alpha coefficients ranging from 0.79 to 0.93 . Construct validity was assessed by correlating the MFI-20 to activities of daily living , anxiety and depression . Significant relations were assumed . Convergent validity was investigated by correlating the MFI scales with a visual analogue scale measuring fatigue and with a fatigue-scale derived from the Rotterdam Symptom Checklist . Results support the validity of the MFI-20 . The highly similar results in the Dutch and Scottish sample suggest that the portrayal of fatigue using the MFI-20 is quite robust Although inflammatory bowel disease ( IBD ) affects patients ' psychological well-being , previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life . Therefore , we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills , delivered in an interactive manner , and evaluated it in a large , cluster-r and omized trial . We assigned 540 rehabilitation in patients suffering from IBD ( mean age 43 years , 66 % female ) to either the new intervention or a control group comprising the same overall intensity and the same medical information , but only general psychosocial information . The primary outcome was patient-reported IBD-related concerns . Secondary outcomes included disease knowledge , coping , self-management skills , fear of progression , anxiety , depression and quality of life . Assessment s took place at baseline , end of rehabilitation and after 3 and 12 months . The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes . However , positive changes over time occurred in both groups regarding most outcomes . The superior effectiveness of the newly developed psychoeducational program could not be demonstrated . Since the intervention and control groups may have been too similar , this trial may have been too conservative to produce between-group effects Abstract Background and Aims : Previous studies have shown that antidepressants reduce inflammation in animal models of colitis . The present trial aim ed to examine whether fluoxetine added to st and ard therapy for Crohn ’s disease [ CD ] maintained remission , improved quality of life [ QoL ] and /or mental health in people with CD as compared to placebo . Methods : A parallel r and omized double-blind placebo controlled trial was conducted . Participants with clinical ly established CD , with quiescent or only mild disease , were r and omly assigned to receive either fluoxetine 20 mg daily or placebo , and followed for 12 months . Participants provided blood and stool sample s and completed mental health and QoL question naires . Immune functions were assessed by stimulated cytokine secretion [ CD3/CD28 stimulation ] and flow cytometry for cell type . Linear mixed-effects models were used to compare groups . Results : Of the 26 participants , 14 were r and omized to receive fluoxetine and 12 to placebo . Overall , 14 [ 54 % ] participants were male . The mean age was 37.4 [ SD=13.2 ] years . Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn ’s Disease Activity Index [ F(3 , 27.5)=0.064 , p=0.978 ] or faecal calprotectin [ F(3 , 32.5)=1.08 , p=0.371 ] , but did have modest effects on immune function . There was no effect of fluoxetine on physical , psychological , social or environmental QoL , anxiety or depressive symptoms as compared to placebo [ all p>0.05 ] . Conclusions : In this small pilot clinical trial , fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ ID : ACTRN12612001067864 . BACKGROUND & AIMS Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis . Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis . METHODS We evaluated the efficacy of granulocyte/monocyte apheresis in a r and omized , double-blind , sham-controlled trial in patients with active moderate-to-severe ulcerative colitis ( Mayo score 6 - 11 ) in community-based and tertiary care centers . As intervention , we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System ( JIMRO , Ltd , Takasaki , Japan ) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study ( N = 168 ) and in a smaller , companion study of identical design conducted in Europe and Japan ( N = 47 ) . RESULTS In the pivotal study , clinical remission rates ( Mayo score 0 - 2 , with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination ) were 17 % and 11 % for the granulocyte/monocyte apheresis ( n = 112)- and sham-treatment groups , respectively ( n = 56 ; P = .361 ) . Clinical response ( Mayo score reduction of > /=3 points from baseline ) was observed in 44 % and 39 % of patients , respectively ( P = .620 ) . Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response , and changes in Mayo and quality -of-life scores . The companion study and pooled data from both studies also yielded similar results . CONCLUSIONS In this study , granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug OBJECTIVE This study vali date d a brief measure of fatigue in rheumatoid arthritis ( RA ) , the Functional Assessment of Chronic Illness Therapy ( FACIT ) Fatigue Scale . METHODS The FACIT Fatigue was tested along with measures previously vali date d in RA : the Multidimensional Assessment of Fatigue ( MAF ) and Medical Outcomes Study Short-Form 36 ( SF-36 ) Vitality . The sample included 636 patients with RA enrolled in a 24 week double blind , r and omized clinical trial ( RCT ) of adalimumab versus placebo . RESULTS The FACIT Fatigue showed good internal consistency ( alpha = 0.86 to 0.87 ) , strong association with SF-36 Vitality ( r = 0.73 to 0.84 ) and MAF ( r = -0.84 to -0.88 ) , and the ability to differentiate patients according to clinical change using the American College of Rheumatology ( ACR ) response criteria ( ACR 20/50/70 ) . Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures . A minimally important difference in FACIT Fatigue change score of 3 - 4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo . CONCLUSION The FACIT Fatigue is a brief , valid measure for monitoring this important symptom and its effects on patients with RA BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis . We compared the efficacy of early treatment ( within 6 months after diagnosis ) with azathioprine versus conventional management of patients at high risk for disabling disease . METHODS We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease . From July 2005 to November 2010 , patients at 24 French centers were r and omly assigned to treatment with azathioprine ( 2.5 mg ∙ kg(-1 ) ∙ day(-1 ) , n = 65 ) or conventional management ( azathioprine only in cases of corticosteroid dependency , chronic active disease with frequent flares , poor response to corticosteroids , or development of severe perianal disease ) ( n = 67 ) . The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion . RESULTS During the 3-year follow-up period , 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy . Forty-one patients in the conventional management  group required immunosuppressant therapy  ( 61 % ; median time to first prescription , 11 months ) . In the azathioprine group , a median 67 % of trimesters were spent in remission ( interquartile range , 11%-85 % ) compared with 56 % in the conventional management group ( interquartile range , 29%-73 % ) ( P = .69 ) . Among secondary outcomes , a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group ( 96 % ± 3 % and 82 % ± 6 % at month 36 , respectively ; P = .036 ) . The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups . CONCLUSIONS Based on results from a clinical trial , administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission . Clinical trials.gov , Number NCT00546546 Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn 's disease ( CD ) . Design R and omised , double-blind , placebo controlled trial in eight Dutch hospitals . In total , 76 CD patients with active perianal fistulising disease were enrolled . After adalimumab induction therapy ( 160/80 mg week 0 , 2 ) , patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks . After 12 weeks , adalimumab was continued . Follow-up was 24 weeks . Primary endpoint ( clinical response ) was defined as 50 % reduction of fistulas from baseline to week 12 . Secondary endpoints included remission ( closure of all fistulas ) , Perianal Crohn 's Disease Activity Index , Crohn 's Disease Activity Index ( CDAI ) and Inflammatory Bowel Disease Question naire ( IBDQ ) . Results Clinical response was observed in 71 % of patients treated with adalimumab plus ciprofloxacin and in 47 % treated with adalimumab plus placebo ( p=0.047 ) . Likewise , remission rate at week 12 was significantly higher ( p=0.009 ) in the combination group ( 65 % ) compared with adalimumab plus placebo ( 33 % ) . Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 ( p=0.005 and p=0.009 , respectively ) . At week 24 , no difference in clinical response between the two treatment groups was observed ( p=0.22 ) . No difference in safety issues was observed . Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD . However , after discontinuation of antibiotic therapy , the beneficial effect of initial coadministration is not maintained . Trial registration Clinical Trials.gov Identifier : NCT00736983 Objective The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn 's disease ( CD ) inadequately responsive to concomitant therapies . Methods We examined responses to the Inflammatory Bowel Disease Question naire ( IBDQ ) from patients enrolled in a previously reported , r and omized , placebo-controlled study . Patients with active CD received a single intravenous infusion of either placebo or infliximab 5 , 10 , or 20 mg/kg . Most patients received stable doses of mesalamine , corticosteroids , azathioprine , or 6-mercaptopurine throughout the study . Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared . Results Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks ( p < 0.001 ) . Infliximab-treated patients also had larger improvements in all IBDQ dimensions : bowel ( p = 0.007 ) , social ( p = 0.002 ) , emotional ( p < 0.001 ) , and systemic ( p < 0.001 ) . A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week ( p < 0.001 ) , full or a lot of energy ( p = 0.019 ) , and no or hardly any difficulty doing leisure or sports activities ( p = 0.011 ) , and being extremely or very satisfied with their personal life ( p = 0.046 ) . They also significantly differed in responses regarding fatigue , frustration , ability to work , general well-being , depression , anxiety , and anger result ing from bowel problems . Conclusions These results indicate that infliximab significantly improved quality of life in patients with active CD , increasing their ability to work and participate in leisure activities , and decreasing feelings of fatigue , depression , and anger Background : Iron deficiency anemia ( IDA ) is frequently seen in inflammatory bowel disease . Traditionally , oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation . This multicenter phase-3 study tested the efficacy and safety of ferric maltol , a complex of ferric ( Fe3 + ) iron with maltol ( 3-hydroxy-2-methyl-4-pyrone ) , as a novel oral iron therapy for IDA . Methods : Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn 's disease , mild-to-moderate IDA ( 9.5–12.0 g/dL and 9.5–13.0 g/dL in females and males , respectively ) , and documented failure on previous oral ferrous products received oral ferric maltol capsules ( 30 mg twice a day ) or identical placebo for 12 weeks according to a r and omized , double-blind , placebo-controlled study design . The primary efficacy endpoint was change in hemoglobin ( Hb ) from baseline to week 12 . Safety and tolerability were assessed . Results : Of 329 patients screened , 128 received r and omized therapy ( 64 ferric maltol-treated and 64 placebo-treated patients ) and comprised the intent-to-treat efficacy analysis : 55  ferric maltol patients ( 86 % ) and 53 placebo patients ( 83 % ) completed the trial . Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4 , 8 , and 12 : mean ( SE ) 1.04 ( 0.11 ) g/dL , 1.76 ( 0.15 ) g/dL , and 2.25 ( 0.19 ) g/dL , respectively ( P < 0.0001 at all time-points ; analysis of covariance ) . Hb was normalized in two-thirds of patients by week 12 . The safety profile of ferric maltol was comparable with placebo , with no impact on inflammatory bowel disease severity . Conclusions : Ferric maltol provided rapid clinical ly meaningful improvements in Hb and showed a favorable safety profile , suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease Ferric maltol was effective and well‐tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12‐week placebo‐controlled trial Background Crohn 's disease ( CD ) and multiple sclerosis ( MS ) share common pathogenic processes . Interferon ( IFN ) beta-1a is effective and generally well tolerated in patients with MS and has been shown to down-regulate the expression of interleukin-12 , a cytokine that is thought to be involved in mucosal degeneration in CD . IFN beta-1a therefore offers promise as a treatment for CD . Methods In this multicentre , double-blind , placebo-controlled , phase II , dose-finding study , patients with steroid-induced clinical remissions of CD were r and omized 1:1:1:1 to subcutaneous IFN beta-1a : 66 mcg three times weekly ( tiw ) , 44 mcg tiw , 44 mcg twice weekly ( biw ) , or matching placebo tiw with steroid tapering . The primary endpoint was the proportion of patients relapse-free at Week 26 . Safety was also assessed . Results This study was terminated early following a planned interim analysis at 26 weeks . Of the planned 192 patients , 67 were r and omized to treatment : placebo ( n = 16 ) , or IFN beta-1a 44 mcg biw ( n = 17 ) , 44 mcg tiw ( n = 16 ) or 66 mcg tiw ( n = 18 ) . In total , 20/67 patients ( 29.9 % ) completed 26 weeks and 7 patients ( 10.4 % ) completed 52 weeks . The proportion of patients who remained relapse-free at Week 26 did not differ significantly between the placebo group ( 5/16 , 31 % ) and the IFN beta-1a 44 mcg biw ( 6/17 , 35 % ; p = 0.497 ) , 44 mcg tiw ( 7/16 , 44 % ; p = 0.280 ) or 66 mcg tiw ( 2/18 , 11 % ; p = 0.333 ) groups . There was little difference between treatment groups in secondary efficacy endpoints . IFN beta-1a was generally well tolerated at all doses . Adverse events ( AEs ) were generally mild or moderate in IFN beta-1a-treated patients , with the most common AEs ( influenza-like symptoms , headache , injection-site reactions ) being similar to those reported with IFN beta-1a in MS . Conclusion There was no difference in efficacy between patients with CD receiving IFN beta-1a or placebo .  However , these results should be considered in the context of the low patient numbers and high dropout rate . Overall , IFN beta-1a was generally well tolerated , with a safety profile that was consistent with previous experience in MS.Trial registration Clinical Trials.gov Introduction Iron deficiency anemia ( IDA ) is common in patients with gastrointestinal ( GI ) disorders and can adversely affect quality of life .  Oral iron is poorly tolerated in many patients with GI disorders . Ferumoxytol is approved for the intravenous treatment of IDA in patients with chronic kidney disease . This study aim ed to evaluate the efficacy and safety of ferumoxytol in patients with IDA and concomitant GI disorders . Patients and methods This analysis included 231 patients with IDA and GI disorders from a Phase III , r and omized , double-blind , placebo-controlled trial evaluating ferumoxytol ( 510 mg ×2 )  versus placebo in patients who had failed or were intolerant of oral iron therapy . The primary study end point was the proportion of patients achieving a ≥20 g/L increase in hemoglobin ( Hgb ) from baseline to Week 5 . Other end points included mean change in Hgb , proportion of patients achieving Hgb ≥120 g/L , mean change in transferrin saturation , and patient-reported outcomes ( PROs ) . Results Significantly more patients with IDA  receiving ferumoxytol achieved a ≥20 g/L increase in Hgb  versus placebo ( 82.1 % vs 1.7 % , respectively ; P<0.001 ) . Mean increase in Hgb ( 28.0 g/L vs −1.0 g/L , respectively ; P<0.001 ) significantly favored ferumoxytol treatment . Ferumoxytol-treated patients demonstrated significantly greater improvements than placebo-treated patients relative to their very poor baseline PRO scores posttreatment , including improvements in the Functional Assessment of Chronic Illness Therapy – Fatigue question naire and various domains of the 36-Item Short-Form Health Survey . Ferumoxytol-treated patients had a low rate of adverse events . Conclusion In this study , ferumoxytol was shown to be an efficacious and generally well-tolerated treatment option for patients with IDA and underlying GI disorders who were unable to use or had a history of unsatisfactory oral iron therapy Background Ingestion of And oSan ™ , based on the mushroom Agaricus blazei Murill , has previously been shown to exhibit anti-inflammatory effects because of reduction of pro-inflammatory cytokines in healthy individuals and patients with ulcerative colitis . In this r and omized single-blinded placebo controlled study we examined whether intake of And oSan ™ also result ed in clinical effects . Methods and Findings 50 patients with symptomatic ulcerative colitis were block-r and omized and blinded for oral daily intake of And oSan ™ or placebo for the 21 days ’ experimental period . The patients reported scores for symptoms , fatigue and health related quality of life ( HRQoL ) at days 0 , 14 and 21 . Fecal calprotectin and general blood parameters were also analyzed . In the And oSan ™ group ( n = 24 ) symptoms improved from baseline ( day 0 ) to days 14 and 21 , with respective mean scores ( 95 % CI ) of 5.88 ( 4.92–6.83 ) , 4.71 ( 3.90–5.52 ) ( p = 0.002 ) and 4.50 ( 3.70–5.30 ) ( p = 0.001 ) . Corresponding improved mean scores ( ±SD ) for total fatigue were 16.6 ( 5.59 ) , 14.1 ( 4.50 ) ( p = 0.001 ) and 15.1 ( 4.09 ) ( p = 0.023 ) . These scores in the placebo group ( n = 26 ) were not improved . When comparing the two study groups using mixed model statistics , we found significant better scores for the And oSan ™ - patients . HRQoL for dimensions bodily pain , vitality , social functioning and mental health improved in the And oSan ™ group . There were no alterations in general blood sample s and fecal calprotectin . Conclusions Beneficiary effects on symptoms , fatigue and HRQoL from And oSan ™ consumption were demonstrated in this per- protocol study , supporting its use as a supplement to conventional medication for patients with mild to moderate symptoms from ulcerative colitis . The patients did not report any harms or unintended effects of And oSan ™ in this study . Trial Registration Clinical Trials.gov BACKGROUND & AIMS Although antibiotics are frequently used to treat Crohn 's disease , this practice is not supported by strong evidence from r and omized trials . METHODS We conducted a double-blind multicenter study of patients with active Crohn 's disease of the ileum , right colon , or both . Patients were r and omized to receive oral ciprofloxacin and metronidazole , both 500 mg twice daily , or placebo for 8 weeks . All patients received oral budesonide 9 mg once daily . The primary efficacy measure was the proportion of patients in remission at week 8 . RESULTS Of the 134 patients who were r and omized , 130 were evaluated for efficacy ; 66 received placebo , and 64 received antibiotics . At week 8 , 21 patients ( 33 % ) assigned to antibiotics were in remission as compared with 25 patients ( 38 % ) in the placebo group ( P = 0.55 ; absolute difference , -5 % ; 95 % confidence interval , -21 % to 11 % ) . An interaction ( P = 0.025 ) between treatment allocation and disease location on treatment response was identified . Among patients with disease of the colon , 9 of 17 ( 53 % ) were in remission after treatment with antibiotics , compared with 4 of 16 ( 25 % ) of those who received placebo ( P = 0.10 ) . Discontinuation of therapy because of adverse events occurred in 13 of 66 ( 20 % ) patients treated with antibiotics , compared with 0 of 68 in the group who received placebo ( P < 0.001 ) . CONCLUSIONS In patients with active Crohn 's disease of the ileum , the addition of ciprofloxacin and metronidazole to budesonide is an ineffective intervention , but this antibiotic combination may improve outcome when there is involvement of the colon OBJECTIVES : We evaluated the effects of adalimumab maintenance therapy on health-related quality of life ( HRQOL ) in patients with moderate to severe Crohn 's disease . METHODS : In a Phase III , r and omized , double-blind clinical trial ( CHARM ) of moderate to severe Crohn 's disease patients , HRQOL outcomes were compared between the adalimumab maintenance treatment groups ( every other week and weekly injection ) and the adalimumab induction-only group .  The Zung Self-Rating Depression Scale , functional assessment of chronic illness therapy (FACIT)-Fatigue , visual analog pain scales , Inflammatory Bowel Disease question naire ( IBDQ ) , and Medical Outcomes Study 36-item Short Form Health Survey ( SF-36 ) were analyzed for 499 r and omized responders ( a decrease of ≥70 points from baseline in the Crohn 's Disease Activity Index [ CDAI ] ) at baseline and weeks 4 , 12 , 26 , and 56 . RESULTS : CHARM patients  ' HRQOL was substantially impaired at baseline . Following a 4-week adalimumab induction therapy , patients experienced statistically significant improvements in all HRQOL measures ( P < 0.0001 ) . Compared with patients who were assigned to placebo after induction therapy , patients who continued adalimumab at 40 mg every other week maintenance therapy reported less depression ( P < 0.01 ) , fewer fatigue symptoms ( P < 0.001 ) , greater improvements in the IBDQ ( P < 0.05 ) , greater SF-36 physical component summary scores ( P < 0.05 ) , and less abdominal pain ( P < 0.05 ) from weeks 12 to 56 . They also had greater SF-36 mental component summary scores at week 56 ( P < 0.05 ) . Patients who continued adalimumab at 40-mg weekly maintenance therapy reported less depression and fewer fatigue symptoms at week 56 , greater improvement in IBDQ , and less abdominal pain from weeks 12 to 56 ( all P < 0.05 vs. placebo ) . CONCLUSIONS : Adalimumab maintenance therapy provided sustained improvements in HRQOL for patients with moderate to severe Crohn 's disease through week 56 BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . Background : There is an unmet need for safe and effective medicines to treat children with Crohn ’s disease . Recently , investigations have shown an association between endogenous opioid peptides and inflammatory cells . Aims : The aims of this study were to evaluate the safety and tolerability of an opioid antagonist , naltrexone , in children with moderate to severe Crohn ’s disease . Methods : A pilot clinical trial was conducted in children with moderate to severe Crohn ’s disease . Fourteen subjects with a mean age of 12.3 years ( range , 8 to 17 y ) were enrolled . Children were r and omized to placebo or naltrexone ( 0.1 mg/kg ) orally for 8 weeks followed by open-labeled treatment with 8 additional weeks of naltrexone .  Safety and toxicity were monitored by physical examinations and blood chemistries . Clinical activity was assessed by the Pediatric Crohn ’s Disease Activity Index ( PCDAI ) and Quality of life was monitored by the Impact III survey . Results : Oral naltrexone was well tolerated without any serious adverse events in children with moderate to severe Crohn ’s disease . PCDAI scores significantly decreased from pretreatment values ( 34.2±3.3 ) with an 8-week course of naltrexone therapy ( 21.7±3.9 ) ( P=0.005 ) . Twenty-five percent of those treated with naltrexone were considered in remission ( score ⩽10 ) and 67 % had improved with mild disease activity ( decrease in PCDAI score by at least 10 points ) at the end of the study . Systemic and social quality of life improved with naltrexone treatment ( P=0.035 ) . Conclusions : Naltrexone therapy seems safe with limited toxicity when given to children with Crohn ’s disease and may reduce disease activity Background : The use of stress management psychotherapy is hypothesized to produce greater improvement in disease course and disease‐specific quality of life ( IBDQ ) compared to usual medical care alone in patients with ulcerative colitis ( UC ) or Crohn 's disease ( CD ) showing high levels of stress ( based on the Perceived Stress Question naire [ PSQ ] ) . Methods : Fifty‐eight patients with UC and 56 patients with CD who had experienced continuous disease activity or had relapsed over the previous 18 months , with an activity index for UC or CD ≥4 , a PSQ ≥60 , and without serious psychiatric disorders or other serious medical conditions were r and omized to receive either treatment as usual ( TAU ) or TAU plus stress management psychotherapy . Psychotherapy consisted of three group sessions ( psychoeducation , problem‐solving , relaxation ) and 6–9 individual sessions based on cognitive behavior therapy‐related methods with 1–3 booster sessions at 6 and 12 months follow‐up . Gastroenterologists blinded to intervention group assessed disease activity and course at baseline and at 3 , 6 , 12 , and 18 months . Patients completed the IBDQ at baseline , 6 , 12 , and 18 months . Results : The intervention did not improve disease or reduce relapse ; however , it increased the IBDQ score ( P = 0.009 , mean differences 16.3 [ SD 6.1 ] ) . On analysis of UC and CD separately , improvement of IBDQ was only found in the UC group . Conclusions : Stress management psychotherapy does not appear to improve disease course or reduce relapse in patients with IBD . It might improve quality of life , particularly in patients with UC . ( Inflamm Bowel Dis 2011 ; The present study was design ed to assess the effectiveness of techniques of behavioural assessment and treatment of Crohn 's disease ( CD ) . On the assumption that stress events have a pronounced influence on the life of Crohn 's patients , we proposed stress management treatment . This is intended to control stress and improve patients ' personal and social competence .  Forty-five patients with Crohn 's disease were r and omly assigned to one of three treatment groups , two experimental groups : stress management and self-directed stress management , and a control group : conventional medical treatment . The subjects underwent eight individual sessions which were specific to each condition . All subjects completed symptom monitoring diaries . The subjects who received training in stress management experienced a significant post-treatment reduction of tiredness ( P < 0.1 ) , constipation ( P < 0.1 ) , abdominal pain ( P < 0.5 ) and distended abdomen ( P < 0.5 ) . The subjects who received training in self-directed stress management experienced a significant reduction in tiredness ( P < 0.1 ) and abdominal pain ( P < 0.5 ) . No significant changes were observed in symptomatology in the conventional medical treatment group . Similar results were obtained in the 12 month follow-up BACKGROUND & AIMS Tetomilast ( OPC-6535 ) , a novel thiazole compound , inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release . METHODS One hundred eighty-six patients with mildly to moderately active ulcerative colitis ( Disease Activity Index [ DAI ] 4 - 11 points ) from 35 centers were r and omized to receive an oral , once-daily dose of placebo or tetomilast 25 mg or 50 mg for 8 weeks . RESULTS Percentages of patients reaching the primary end point ( improvement as defined by reduction in DAI > or =3 at week 8) were not significantly different between placebo ( 35 % ) and either the 25 mg tetomilast ( 52 % ) or the 50 mg tetomilast ( 39 % ) groups ( intent-to-treat population ) . Remission rates ( DAI 0 - 1 ) were 7 % , 16 % , and 21 % , respectively ( not significant ) . Mean reduction in DAI at week 8 was greater in the 25-mg group than under placebo ( 2.8 + /- 0.4 vs 1.7 + /- 0.36 , respectively , P = .041 ) and approached statistical significance in the 50-mg group ( 2.8 + /- 0.46 , P = .056 ) . A post hoc analysis focusing on patients with high activity scores ( baseline DAI 7 - 11 ) suggested differences between tetomilast and placebo that will require further investigation . No significant safety concerns were raised . Main adverse effects included gastrointestinal problems ( nausea , vomiting ) and were preferentially seen in the 50-mg tetomilast group . CONCLUSIONS This phase II trial of tetomilast in ulcerative colitis did not achieve statistical significance for the primary end point . Secondary end points indicate a potential clinical activity of tetomilast . The post hoc analysis suggests that further clinical development should focus on patients with objective parameters of inflammation Objective : Although treatment with corticosteroids induces remission in Crohn ’s disease , prolonged exposure to corticosteroids is undesirable . This r and omised clinical trial evaluated the efficacy of recombinant human granulocyte – macrophage colony-stimulating factor ( sargramostim ) , an activator of innate immunity , in corticosteroid-dependent patients with Crohn ’s disease . Design : Patients were r and omised in a 2:1 ratio , to sargramostim 6 μg/kg subcutaneously once daily or placebo for up to 22 weeks . The study consisted of ( 1 ) an adjunctive phase ( weeks 1–4 ) in which patients received study drug plus corticosteroid therapy ; ( 2 ) a forced corticosteroid tapering phase ( weeks 4–14 ) ; and ( 3 ) an observation phase ( 4 weeks ) in which patients received study drug plus prednisone ⩽7.5 mg . The primary endpoint was corticosteroid-free remission ( Crohn ’s Disease Activity Index ( CDAI ) ⩽150 ) 4 weeks after corticosteroid elimination . Secondary endpoints were corticosteroid-free response ( CDAI decreased by ⩾100 ) and induction of remission in patients who reduced the dose of corticosteroid to 2.5–7.5 mg . Results : Eighty-seven patients were r and omised to sargramostim and 42 to placebo . Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission ( 18.6 % vs 4.9 % ; p = 0.03 ) . Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5–7.5 mg/day . Sargramostim treatment was also associated with significant improvements in health-related quality of life . Patients who received sargramostim were more likely to experience musculoskeletal pain , injection site reactions and dyspnoea . Conclusions : Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn ’s disease with corticosteroid dependence . Sargramostim may provide significant benefit in this population if these findings are confirmed . Trial registration number : NCT00206596 BACKGROUND & AIMS A r and omized placebo-controlled trial evaluated the efficacy of natalizumab induction therapy in patients with Crohn 's disease . METHODS Patients ( N = 509 ) with moderately to severely active Crohn 's disease and active inflammation characterized by elevated C-reactive protein concentrations were r and omized ( 1:1 ) to receive natalizumab 300 mg or placebo intravenously at Weeks 0 , 4 , and 8 . The primary end point was induction of response ( > or = 70-point decrease from baseline in the Crohn 's Disease Activity Index score at Week 8 sustained through Week 12 ) . Additional efficacy end points included the proportion of patients with sustained remission ( Crohn 's Disease Activity Index score < 150 points ) and response or remission over time . RESULTS Response at Week 8 sustained through Week 12 occurred in 48 % of natalizumab-treated patients and 32 % of patients receiving placebo ( P < .001 ) . Sustained remission occurred in 26 % of natalizumab-treated patients and 16 % of patients receiving placebo ( P = .002 ) . Week 4 response rates were 51 % for natalizumab and 37 % for placebo ( P = .001 ) . Responses remained significantly higher at subsequent assessment s ( P < .001 ) in natalizumab-treated patients . Natalizumab-treated patients also had significantly higher remission rates at Weeks 4 , 8 , and 12 ( P < or = .009 ) . The frequency and types of adverse events were similar between treatment groups . CONCLUSIONS Natalizumab induced response and remission at Week 8 that was sustained through Week 12 . Response and remission rates for natalizumab were superior to those for placebo at Weeks 4 , 8 , and 12 , demonstrating the early and sustained efficacy of natalizumab as induction therapy in patients with elevated C-reactive protein and active Crohn 's disease .  Natalizumab was well tolerated in this study Objective To establish the impairment of different dimensions of quality of life in inflammatory bowel disease ( IBD ) . Design Prospect i ve observational study . Participants 289 patients [ 160 with ulcerative colitis ( UC ) and 129 with Crohn 's disease ( CD ) ] . Measures Health-related quality of life was assessed by means of the  Inflammatory Bowel Disease Question naire ( IBDQ ) and the Psychological General Well Being Index ( PGWBI ) . Results In active IBD , all dimensions of the quality of life scored significantly lower than in inactive IBD , indicating a poor quality of life . Social impairment was the least impaired dimension of the IBDQ in active UC and CD , compared with digestive and systemic symptoms . In inactive IBD , the systemic symptoms domain received the lowest score ( P < 0.01 ) . In a subgroup of 22 patients studied before and after remission , emotional function was the most impaired dimension after achieving remission . The Psychological General Well Being Index was significantly impaired in active UC [ 78.5 ( range 64–89 ) ] and CD [ 76.5 ( range 69–97 ) ] relative inactive IBD [ 104 ( range 93–111 ) ] vs 106 ( 95–113 ) , respectively;P < 0.05 ] . Conclusions Quality of life is impaired in IBD . During relapse , clinicians should pay attention to digestive symptoms and psychological distress . In remission , they should be sensitive to systemic symptoms BACKGROUND The efficacy of vedolizumab , an α4β7 integrin antibody , in Crohn 's disease is unknown . METHODS In an integrated study with separate induction and maintenance trials , we assessed intravenous vedolizumab therapy ( 300 mg ) in adults with active Crohn 's disease . In the induction trial , 368 patients were r and omly assigned to receive vedolizumab or placebo at weeks 0 and 2 ( cohort 1 ) , and 747 patients received open-label vedolizumab  at weeks 0 and 2 ( cohort 2 ) ; disease status was assessed at week 6 . In the maintenance trial , 461 patients who had had a response to vedolizumab  were r and omly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52 . RESULTS At week 6 , a total of 14.5 % of the patients in cohort 1 who received vedolizumab and 6.8 % who received placebo were in clinical remission ( i.e. , had a score on the Crohn 's Disease Activity Index [ CDAI ] of ≤150 , with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity ) ( P=0.02 ) ; a total of 31.4 % and 25.7 % of the patients , respectively , had a CDAI-100 response ( ≥100-point decrease in the CDAI score ) ( P=0.23 ) . Among patients in cohorts 1 and 2 who had a response to induction therapy , 39.0 % and 36.4 % of those assigned to vedolizumab every 8 weeks and every 4 weeks , respectively , were in clinical remission at week 52 , as compared with 21.6 % assigned to placebo ( P<0.001 and P=0.004 for the two vedolizumab groups , respectively , vs. placebo ) . Antibodies against vedolizumab developed in 4.0 % of the patients . Nasopharyngitis occurred more frequently , and headache and abdominal pain less frequently , in patients receiving vedolizumab than in patients receiving placebo . Vedolizumab , as compared with placebo , was associated with a higher rate of serious adverse events ( 24.4 % vs. 15.3 % ) , infections ( 44.1 % vs. 40.2 % ) , and serious infections ( 5.5 % vs. 3.0 % ) . CONCLUSIONS  Vedolizumab-treated patients with active Crohn 's disease were more likely than patients receiving placebo to have a remission , but not a CDAI-100 response , at week 6 ; patients with a response to induction therapy who continued to receive vedolizumab ( rather than switching to placebo ) were more likely to be in remission at week 52 . Adverse events were more common with vedolizumab . ( Funded by Millennium Pharmaceuticals ; GEMINI 2 Clinical Trials.gov number , NCT00783692 . ) 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 . ) BACKGROUND Polymeric feeds have shown variable efficacy in active Crohn 's disease ( CD ) with remission rates from 36 % to 82 % . Meta-analyses of elemental , peptide , and whole protein feeds have shown a strong negative correlation between remission rate in CD and the long chain triglyceride ( LCT ) content of the feed . We performed a r and omised controlled double blind trial in patients with active CD comparing two single whole protein feeds with LCT supplying 5 % or 30 % of the total energy . METHODS Fifty four patients with active CD ( Crohn 's disease activity index ( CDAI ) > 200 , serum C reactive protein ( CRP ) 10 mg/l ) were r and omised to a high or low LCT feed for three weeks  . The total amount of energy supplied by fat was identical in the two feeds . Remission was defined as a CDAI ⩽150 and response as a fall in CDAI of ⩾70 or a CRP < 10 mg/l . RESULTS Overall remission rate by intention to treat was 26 % for the low LCT feed and 33 % for the high LCT feed ( p=0.38 ) . Response was achieved in 33 % with the low LCT and in 52 % with the high LCT feed ( p=0.27 ) . CRP < 10 mg/l was achieved in 30 % in the low LCT and 33 % in the high LCT group ( p=0.99 ) . Thirty nine per cent ( 21/54 ) of patients withdrew before three weeks because of inability to tolerate the diet . Excluding patients unable to tolerate the diet , remission rates were 46 % for low LCT and 45 % for high LCT ( p=0.99 ) . DISCUSSION This trial has shown no difference in the effect of low and high LCT whole protein feeds in active CD . The previously reported correlation between LCT content of diet and response in active CD is unlikely to be due to LCT itself and may be due to some other component of high LCT feeds Background and Aims The GEMINI long-term safety [ LTS ] study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab , an α4β7 integrin antagonist for ulcerative colitis [ UC ] and Crohn 's disease . We provide an interim analysis of efficacy in patients with UC . Methods Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naïve patients received open-label vedolizumab  every 4 weeks . Interim data were collected from May 22 , 2009 to June 27 , 2013 . Clinical response and remission , evaluated using partial Mayo scores , and health-related quality of life [ HRQL ] were assessed for up to 152 weeks of cumulative treatment in the efficacy population . Results As of June 27 , 2013 , 63 % of the efficacy population [ n = 532/845 ] were continuing treatment . Among patients who responded to vedolizumab  induction and had data available , 88 % [ n = 120/136 ] were in remission after 104 weeks of exposure ( 96 % [ n = 70/73 ] after 152 weeks ) . Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI 1 [ n = 32 ] before week 52 , increased dosing to every 4 weeks in GEMINI LTS result ed in response and remission rates of 41 % and 28 % , respectively , after 52 weeks , an increase from 19 % and 6 % , respectively , from before the dose increase . Similar benefits were demonstrated regardless of prior tumour necrosis factor-antagonist exposure . Durable benefits on HRQL were also observed . Conclusions Patients with UC experienced clinical and HRQL improvements with continued vedolizumab treatment . Increased dosing frequency to every 4 weeks was beneficial in patients who had loss of response to 8-weekly dosing Background Elective switching between anti-tumour necrosis factor ( TNF ) agents not necessarily dictated by efficacy or tolerability occurs in clinical practice . A study was undertaken to evaluate prospect ively the impact of elective switching of patients with Crohn 's disease well controlled with intravenous infliximab  to subcutaneous adalimumab in a controlled trial . Methods An open-label r and omised single-centre trial recruited 73 patients with ongoing response to at least 6 months of scheduled maintenance infliximab . Patients were r and omised to continue intravenous 5 mg/kg infliximab or to switch to subcutaneous adalimumab 80 mg at baseline followed by 40 mg every other week for 1 year . Dose optimisation was allowed for intermittent flares , and patients with loss of response or intolerance could cross over to the alternative treatment group . Tolerability , patient preference and efficacy of both treatment options were the primary outcomes . Results Dose optimisation or interruption of treatment occurred in 17/36 patients ( 47 % ) in the adalimumab group and in 6/37 patients ( 16 % ) in the infliximab group ( p=0.006 ) . One patient interrupted infliximab treatment and 10 patients interrupted adalimumab treatment ( p=0.003 ) , mostly for loss of tolerance . Overall , patients preferred adalimumab treatment . All five serious adverse events were related to complicated Crohn 's disease and occurred in patients r and omised to adalimumab . Injection site reactions were more frequent than infusion reactions ( 8 vs 1 , p=0.01 ) , but only the latter caused cessation of further dosing . Anti-TNF serum levels were stable throughout the 1-year period in both groups . Conclusion Elective switching from infliximab to adalimumab is associated with loss of tolerance and loss of efficacy within 1 year . Adherence to the first anti-TNF agent is recommended Objectives Activated granulocytes and monocytes may contribute to the pathogenesis of Crohn 's disease ( CD ) . In small , uncontrolled studies , granulocyte/monocyte apheresis ( GMA ) has shown promise in treating CD . We conducted a r and omised , double-blind study to compare GMA with a sham procedure in patients with moderate to severe CD . Design Patients with active CD as defined by a Crohn 's Disease Activity Index ( CDAI ) of 220–450 were r and omly allocated in a 2:1 ratio to treatment with GMA using the Adacolumn Apheresis System ( JIMRO , Takasaki , Japan ) or sham apheresis . Ten apheresis sessions were scheduled over a 9-week period , and efficacy was evaluated at week 12 . The primary end point was the proportion of patients achieving clinical remission ( CDAI score ≤150 without use of prohibited drugs ) . Results Clinical remission was achieved by 17.8 % of patients in the GMA group ( n=157 ) compared with 19.2 % of those in the sham control group ( n=78 ) ( absolute difference −1.4 % ( 95 % CI−12.8 % to 8.5 % ) , p=0.858 ) . Clinical response ( defined as a ≥100-point decrease in CDAI ) was achieved by 28.0 % and 26.9 % of patients in the GMA and sham groups , respectively ( p=1.000 ) . The two treatments produced similar changes from baseline in CDAI and quality of life , as well as in disease severity assessed endoscopically . The incidence and types of adverse events did not differ between groups . Conclusions GMA was well tolerated , but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD . Clinical trial registration number Clinical Trials.gov identifier NCT00162942 Objective To assess the effectiveness of solution-focused therapy ( SFT ) on fatigue and quality of life ( QoL ) in patients with fatigued inflammatory bowel disease ( IBD ) . Design R and omised controlled trial in two Dutch hospitals . Patients with IBD with quiescent IBD and with a Checklist Individual Strength — Fatigue ( CIS — fatigue ) score of ≥35 were enrolled . Patients were 1:1 r and omised to receive SFT or care as usual ( CAU ) for 3 months . Patients were followed for a further 6 months after the SFT . Primary endpoint was defined as changes in fatigue and QoL during follow-up . Secondary endpoints included change in anxiety and depression , medication use , side effects to medication , disease activity , laboratory parameters ( C-reactive protein , leucocytes and haemoglobin ) and sleep quality . Results Ninety-eight patients were included , of whom 63 % were women , mean age was 40.1 years . After the SFT course , 17 ( 39 % ) patients in the SFT group had a CIS-fatigue score below 35 compared with eight ( 18 % ) of patients in the CAU group ( p=0.03 ) . The SFT group also showed a greater reduction in fatigue across the first 6 months compared with the CAU group ( CIS-fatigue : p=<0.001 and CIS-total : p=0.001 ) . SFT was associated with a significant higher mean IBD question naire change at 3 months ( p=0.020 ) . At 9 months , no significant differences between the two groups were observed . Conclusions SFT has a significant beneficial effect on the severity of fatigue and QoL in patients with quiescent IBD . However , this effect diminished during follow-up
BACKGROUND Inflammatory bowel disease ( IBD ) is an umbrella term used to describe a group of chronic , progressive inflammatory disorders of the digestive tract .
Crohn 's disease and ulcerative colitis are the two main types .
Fatigue is a common , debilitating and burdensome symptom experienced by individuals with IBD .
The subjective , complex nature of fatigue can often hamper its management .
The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies .
OBJECTIVES To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment , placebo or active comparator .