Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. The Effects of Infliximab Therapy on Health-Related Quality of Life in Ulcerative Colitis Patients Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial Reviewing studies with diverse designs: the development and evaluation of a new tool. Current issues in the design of clinical trials in IBD. Health-Related Quality of Life During Natalizumab Maintenance Therapy for Crohn's Disease Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes Self-reported Disability in Patients with Inflammatory Bowel Disease Largely Determined by Disease Activity and Illness Perceptions Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. Randomised clinical trial: a placebo‐controlled study of intravenous golimumab induction therapy for ulcerative colitis Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis On clinical trials with a high placebo response rate Adalimumab for the induction and maintenance of clinical remission in Japanese patients with Crohn's disease. Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFα, improves health-related quality of life in patients with moderate to severe Crohn’s disease Effects of Adalimumab Maintenance Therapy on Health-Related Quality of Life of Patients With Crohn's Disease: Patient-Reported Outcomes of the CHARM Trial Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Natalizumab for active Crohn's disease. Efficacy and tolerability of oral budesonide in Japanese patients with active Crohn's disease: a multicentre, double-blind, randomized, parallel-group Phase II study. Comparison of Two Adalimumab Treatment Schedule Strategies for Moderate-to-Severe Crohn's Disease: Results From the CHARM Trial Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double‐blind, placebo‐controlled, multiple‐dose study Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial Quality of Life Rapidly Improves with Budesonide Therapy for Active Crohn's Disease Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 study Repifermin (keratinocyte growth factor‐2) for the treatment of active ulcerative colitis: a randomized, double‐blind, placebo‐controlled, dose‐escalation trial Clinically Meaningful Improvement in Health-Related Quality of Life in a Randomized Controlled Trial of Certolizumab Pegol Maintenance Therapy for Crohn's Disease The effects of infliximab maintenance therapy on health-related quality of life Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.
BACKGROUND & AIMS Thiazolidinedione lig and s for the gamma subtype of peroxisome proliferator-activated receptors ( PPARgamma ) , widely used to treat type 2 diabetes mellitus , have been proposed as novel therapies for ulcerative colitis ( UC ) . METHODS This multicenter , r and omized , double-blind , placebo-controlled clinical trial compared the efficacy of rosiglitazone ( Av and ia ; GlaxoSmithKline , Philadelphia , PA ) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC .  Disease activity was measured with the Mayo score . The primary end point was clinical response ( > /=2-point reduction ) at week 12 . Clinical remission ( Mayo score < /=2 ) , endoscopic remission , and quality of life were secondary outcomes . RESULTS After 12 weeks of therapy , 23 patients ( 44 % ) treated with rosiglitazone and 12 patients ( 23 % ) treated with placebo achieved clinical response ( P = .04 ) . Remission was achieved in 9 patients ( 17 % ) treated with rosiglitazone and 1 patient ( 2 % ) treated with placebo ( P = .01 ) . Endoscopic remission was uncommon in either treatment arm ( 8 % rosiglitazone vs 2 % placebo ; P = .34 ) . Clinical improvement was evident as early as 4 weeks after beginning treatment ( P = .049 ) . Quality of life was improved significantly at week 8 ( P = .01 ) , but not at week 4 ( P = .48 ) or week 12 ( P = .14 ) . Serious adverse events were rare . CONCLUSIONS Rosiglitazone was efficacious in the treatment of mild to moderately active UC OBJECTIVES : The impact of infliximab induction and maintenance therapy on health-related quality of life ( HRQL ) was evaluated in patients with ulcerative colitis ( UC ) . METHODS : In two placebo-controlled , double-blind studies ( the Active Ulcerative Colitis Trials 1 and 2 [ ACT 1 and 2 ] ) , 728 patients were r and omized to placebo or infliximab 5 mg/kg or 10 mg/kg . Infusions were administered at weeks 0 , 2 , 6 , and every 8 wk thereafter , up to week 22 ( ACT 2 ) or 46 ( ACT 1 ) . Changes in Inflammatory Bowel Disease Question naire ( IBDQ ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary ( PCS and MCS , respectively ) scores were analyzed . RESULTS : Baseline scores for the pooled patient population indicated substantial impairment in HRQL . Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg ( 40 , P < 0.001 ) and 10-mg/kg ( 36 , P < 0.001 ) groups compared with the placebo group ( 28 ) . Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS ( 6.8 and 5.9 , respectively ) and MCS ( 5.9 and 6.4 , respectively ) compared with placebo ( PCS = 3.7 , MCS = 3.0 , P < 0.01 for all comparisons ) . Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy ( P < 0.001 for all comparisons ) . Improvement in total IBDQ score correlated significantly ( P < 0.001 ) with improvement in both PCS and MCS scores , and Mayo score . CONCLUSIONS : Infliximab therapy substantially improved HRQL  in patients with UC . This benefit was sustained through 1 yr with maintenance infliximab therapy Background Placebo medications , by definition , are composed of inactive ingredients that have no physiological effect on symptoms . Nonetheless , administration of placebo in r and omized controlled trials ( RCTs ) and in clinical setting s has been demonstrated to have significant impact on many physical and psychological complaints . Until recently , conventional wisdom has suggested that patients must believe that placebo pills actually contain ( or , at least , might possibly contain ) active medication in order to elicit a response to placebo . However , several recent RCTs , including patients with irritable bowel syndrome ( IBS ) , chronic low back pain , and episodic migraine , have demonstrated that individuals receiving open-label placebo ( OLP )  can still experience symptomatic improvement and benefit from honestly described placebo treatment . Methods and design This paper describes an innovative multidisciplinary trial design ( n = 280 ) that attempts to replicate and exp and upon an earlier IBS OLP study . The current study will compare OLP to double-blind placebo ( DBP ) administration which is made possible by including a nested , double-blind RCT comparing DBP and peppermint oil . The study also examines possible genetic and psychological predictors of OLP and seeks to better underst and participants ’ experiences with OLP and DBP through a series of extensive interviews with a r and omly selected subgroup . Discussion OLP treatment is a novel strategy for ethically harnessing placebo effects . It has potential to re-frame theories of placebo and to influence how physicians can optimize watch- and -wait strategies for common , subjective symptoms . The current study aims to dramatically exp and what we know about OLP by comparing , for the first time , OLP and DBP administration . Adopting a unique , multidisciplinary approach , the study also explores genetic , psychological and experiential dimensions of OLP . The paper ends with an extensive discussion of the “ culture ” of the trial as well as potential mechanisms of OLP and ethical implication s . Trial registration Clinical Trials.gov , identifier : NCT02802241 . Registered on 14 June 2016 UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a  quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The  16-item quality assessment tool ( QATSDD )  was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers .  Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work Although the r and omized controlled trial has become the st and ard for regulatory approval of new drugs and devices in inflammatory bowel disease ( IBD ) , the components of effective trial design and implementation are still evolving . While induction and maintenance of remission are the ultimate goals in the treatment of IBD , the conduct of trials intended to measure these outcomes has varied substantially over time , as have the definitions of disease remission . Significant progress has been made in recent years towards underst and ing patient- and disease-related factors that are essential considerations in clinical trial design . However , questions remain regarding the best methods for assessing disease activity , and importantly for establishing trial end points that are clinical ly relevant and likely to affect meaningful long-term improvements in disease outcomes . This chapter will discuss the current ' best methods ' in IBD trial design and introduce potential future concepts for improving the efficiency of clinical trials as well as their utility to inform clinical practice management OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy Background Tofacitinib , a novel , oral Janus kinase inhibitor , demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis ( UC ) . The objective of the current study was to determine the effect of tofacitinib on patient-reported outcomes ( PROs ) . Methods Eligible patients ( ≥18 years of age ) with a diagnosis of active UC ( total Mayo score of 6 - 12 points and moderately-to-severely active disease on sigmoidoscopy ) were r and omized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg , 3 mg , 10 mg , or 15 mg , or placebo twice daily ( BID ) for 8 weeks . PROs were assessed by the Inflammatory Bowel Disease Question naire ( IBDQ ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact ( IBD PRTI ) survey . Results At Week 8 , mean IBDQ total scores had improved relative to baseline across all five treatment groups ( baseline range 123.2 - 134.5 ; Week 8 range 149.6 - 175.4 ) . Improvement from baseline was significantly greater ( P = 0.001 ) for tofacitinib 15 mg BID versus placebo . For tofacitinib 15 mg BID , most patients reported satisfaction or extreme satisfaction , definite preference for tofacitinib , and definite willingness to use tofacitinib again on the IBD PRTI at week 8 . Patients achieving endoscopic remission ( Mayo endoscopy score of 0 ) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission . Conclusions Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib . The results complement previously reported efficacy and safety data for the Phase II study . ( NCT 00787202 , November 6 , 2008 ) Background : The inflammatory bowel disease ( IBD ) disability index has recently been introduced to measure patients ' physical , psychological , familial , and social limitations associated with IBD . We assessed factors related to self-reported disability and the relationship between disability and direct health care costs . Methods : A large cohort of patients with Crohn 's disease ( CD ) and ulcerative colitis ( UC ) was prospect ively followed for 2 years by 3 monthly web-based question naires . At 2 years , patients completed the IBD disability index , with lower score indicating more disability . Linear regression analysis was used to examine the impact of demographics , clinical characteristics , and illness perceptions on self-reported disability . Trends in direct health care costs across the disability severity groups minimal , mild , moderate , and severe , were tested . Results : A total of 554 patients with CD and 424 patients with UC completed the IBD disability index ( response rate , 45 % ) . Both clinical characteristics and illness perceptions significantly contributed to self-reported disability ( 45%–47 % , P = 0.000 and 8%–12 % , P = 0.000 , respectively ) . Patients with CD scored lower on the self-reported IBD disability index than patients with UC ( 0.255 versus 3.890 , P < 0.000 ) , indicating more disability in patients with CD . Factors independently associated with higher self-reported disability rates were increased disease activity , illness identity ( higher number of symptoms attributed to IBD ) , and stronger emotional response . Disease duration and disease phenotype were not associated with self-reported disability . Direct health care costs increased with the worsening of self-reported disability ( P = 0.000 ) . Conclusions : More disability was reported by patients with CD than by UC . Self-reported disability in IBD was mainly determined by clinical disease activity and illness perceptions but not by disease duration or disease phenotype BACKGROUND & AIMS Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties . We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn 's disease ( CD ) . METHODS A prospect i ve , multicenter , double-blind , placebo-controlled study was conducted in 329 therapy-refractory patients with CD . Clinical improvement was defined by a reduction of the Crohn 's Disease Activity Index ( CDAI ) by 100 points or more and clinical remission by a decrease of the CDAI to < 150 points . At selected centers , patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B ( NF-kappa B ) system was assessed in biopsy specimens . RESULTS Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible , dose-dependent decrease in hemoglobin and thrombocyte counts but no clinical ly significant side effects . No differences in the induction of remission were observed between rhuIL-10 groups ( 1 microg , 18 % [ 9.6 - 29.2 ] ; 4 microg , 20 % [ 11.3 - 32.2 ] ; 8 microg , 20 % [ 11.1 - 31.8 ] ; 20 microg , 28 % [ 18 - 40.7 ] ; and placebo , 18 % [ 9.6 - 29.6 ] ) . Clinical improvement was observed in 46 % ( 33.7 - 59 ) in the 8-microg/kg rhuIL-10 group in comparison with 27 % ( 17 - 39.6 ) in patients taking placebo . Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders . CONCLUSIONS Up to 8 microg/kg of rhuIL-10 was well tolerated . A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group . Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy BACKGROUND & AIMS Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease . This r and omized , double-blind , controlled trial assessed the efficacy and safety of MLN0002 , a monoclonal antibody targeting the alpha4beta7 integrin , in patients with active Crohn 's disease . METHODS Patients were r and omized to receive MLN0002 2.0 mg/kg ( n = 65 ) , MLN0002 0.5 mg/kg ( n = 62 ) , or placebo ( n = 58 ) by intravenous infusion on days 1 and 29 . The primary efficacy end point was clinical response ( > or=70-point decrement in the Crohn 's Disease Activity Index [ CDAI ] score ) on day 57 . Secondary end points were the proportions of patients with clinical remission ( CDAI score < or=150 ) and with an enhanced clinical response ( > or=100-point decrement in CDAI ) . Human anti-human antibody levels were measured . RESULTS Clinical response rates at day 57 were 53 % , 49 % , and 41 % in the MLN0002 2.0 mg/kg , MLN0002 0.5 mg/kg , and placebo groups . Clinical remission rates at day 57 were 37 % , 30 % , and 21 % , respectively ( P = .04 for the 2.0 mg/kg vs placebo comparison ) . At day 57 , 12 % and 34 % of patients in the 2.0- and 0.5-mg/kg groups had clinical ly significant human anti-human antibody levels ( titers > 1:125 ) . There was one infusion-related hypersensitivity reaction . The most common serious adverse event was worsening of Crohn 's disease . CONCLUSIONS This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission .  MLN0002 was well tolerated in patients with active Crohn 's disease Tumour necrosis factor alpha (TNFα)‐antagonism effectively treats ulcerative colitis ( UC ) . The golimumab clinical programme evaluated subcutaneous ( SC ) and intravenous ( IV ) induction , and SC maintenance regimens , in TNFα‐antagonist‐naïve patients with moderate‐to‐severe active UC despite conventional treatment Background Adalimumab is a fully human , monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis ( UC ) . Methods This 52-week , phase 2/3 , r and omized , double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF – naive Japanese patients with UC who were refractory to corticosteroids , immunomodulators , or both . Patients received placebo , adalimumab 80/40 ( 80 mg at week 0 , then 40 mg every other week ) , or adalimumab 160/80 ( 160/80 mg at weeks 0/2 , then 40 mg every other week ) in addition to background UC therapy . Results At week 8 , remission rates were similar among treatment arms , but more patients treated with adalimumab 160/80 achieved response ( placebo , 35 % ; 80/40 , 43 % ; 160/80 , 50 % ; P = 0.044 for 160/80 vs placebo ) and mucosal healing ( placebo , 30 % ; 80/40 , 39 % ; 160/80 , 44 % ; P = 0.045 for 160/80 vs placebo ) compared with placebo . At week 52 , more patients receiving adalimumab 40 mg every other week achieved response ( 18 vs 31 % ; P = 0.021 ) , remission ( 7 vs 23 % ; P = 0.001 ) , and mucosal healing ( 16 vs 29 % ; P = 0.015 ) compared with placebo . Week 8 response to adalimumab was associated with greater rates of response ( 61 % ) , remission ( 46 % ) , and mucosal healing ( 57 % ) at week 52 relative to the overall population . Rates of serious adverse events were similar between treatment arms . Conclusions Induction with adalimumab 160/80 mg led to early response and mucosal healing . Maintenance adalimumab had greater rates of long-term response , remission , and mucosal healing compared with placebo . No new safety signals were identified The basic problem that causes the frequent failure of a st and ard r and omized parallel placebo-controlled clinical trial with a high placebo response rate is the underestimation of the treatment effect by the observed relative treatment difference . A two-period sequential parallel enrichment design has been proposed where the first period is a st and ard parallel design and at the end of the first period , the placebo non-responders are identified and re-r and omized in the second period . Based on such a design , available methods have primarily focused on testing either the first period treatment null hypothesis or the global null hypothesis defined as the joint period 1 and period 2 treatment effect null hypothesis by a test statistic which is either derived from a combined statistic or defined directly as a weighted z-score where the weights are functions of some population and design parameters satisfying certain power optimality criterion . However , in some cases , it is not clear what their combined statistics are estimating and in others , the combined statistics are estimating the apparent treatment effect ; but generally , there is no discussion of the need to provide a proper assessment of the treatment effect for the intended study population . It should be clear that an appropriate assessment of the treatment effect for the intended study population is critical for the benefit/risk analysis as well as the proper dosage recommendation . Any benefit/risk analysis and dosage recommendation that are based on an apparent treatment effect from a st and ard parallel design such as the first period of a sequential parallel enrichment design tend to underestimate the benefit/risk ratio which in turn may lead to overdosing recommendation . It is the purpose of this paper to introduce the concept of an adjusted treatment effect which is derived by adjusting the apparent treatment effect from the first period of a sequential parallel enrichment design with information from the second period subject to a consistency condition . The adjustment properly compensates for the high placebo response rate . It is proposed that this adjusted treatment effect should be used to assess the treatment effect for the intended study population and should be the basis for the benefit/risk analysis and the dosage recommendation BACKGROUND AND AIMS Adalimumab has been shown to be efficacious and well-tolerated in Western patients with Crohn 's disease . These 2 r and omized , double-blind clinical trials evaluated adalimumab efficacy and safety in Japanese patients with moderate to severe Crohn 's disease . METHODS 90 patients enrolled in the induction trial and were r and omized to receive adalimumab 160/80 mg , adalimumab 80/40 mg or placebo at Weeks 0/2 . At Week 4 , patients who achieved a decrease in CDAI ≥ 70 points versus Baseline entered the maintenance trial and were r and omized to adalimumab 40 mg every other week or placebo for 52 weeks . All other patients received 4 more weeks of blinded adalimumab before entering the open-label portion of the maintenance trial . At/after Week 4 of the maintenance trial , blinded patients who flared/failed to respond entered the open-label portion . Open-label maintenance patients received adalimumab 40 mg every other week with the option of 80 mg every other week for flare/non-response . RESULTS Clinical remission rates at Week 4 in the induction trial were 33.3 % , 17.6 % and 13.0 % in the adalimumab 160/80 mg , adalimumab 80/40 mg and placebo groups , respectively . Maintenance remission rates were 38.1 % for adalimumab and 9.1 % for placebo at Week 52 . Anti-TNF naïve patients achieved greater efficacy than anti-TNF exposed patients . Patients r and omized to adalimumab achieved greater quality of life improvement versus placebo . There were no clinical ly relevant differences in safety between adalimumab and placebo . CONCLUSIONS Adalimumab is effective and well-tolerated for inducing and maintaining clinical remission in Japanese patients with moderate to severe Crohn 's disease Background and aims Certolizumab pegol , a polyethylene glycolated Fc-free Fab ’ was efficacious and well tolerated in patients with moderate-to-severe Crohn ’s disease in a previously reported r and omized , placebo-controlled study . In this paper , we report the effect of certolizumab pegol on health-related quality of life ( HRQoL ) . Material s and methods Patients with moderate-to-severe active Crohn ’s disease ( n = 292 ) received subcutaneous certolizumab pegol 100 , 200 , or 400 mg or placebo at weeks 0 , 4 , and 8 . A post hoc analysis of the intent-to-treat population ( 290 patients with HRQoL data ) assessed HRQoL by evaluating patients ’ responses to the self-administered inflammatory bowel disease question naire ( IBDQ ) at baseline and weeks 2 , 4 , 6 , 8 , 10 , and 12 . Results Patients receiving certolizumab pegol 400 mg at weeks 0 , 4 , and 8 demonstrated , via their IBDQ total score , significantly ( P ≤ 0.05 ) greater improvement in HRQoL from baseline to week 12 and at all other time points compared with placebo . Moreover , HRQoL improved over time in all certolizumab pegol groups , irrespective of baseline C-reactive protein levels . Emotional well-being ( IBDQ Emotional Function domain ) improved throughout the study for patients receiving certolizumab pegol 400 mg . This improvement was significantly ( P ≤ 0.05 ) greater than for patients receiving placebo at all time points . In addition , systemic symptoms ( IBDQ Systemic Symptoms domain ) improved significantly more in patients receiving certolizumab pegol 400 mg than in those receiving placebo at weeks 4 , 8 , 10 , and 12 ( P ≤ 0.05 ) and approached statistical significance at week 2 ( P = 0.054 ) . Conclusion This analysis suggests that certolizumab pegol 400 mg improves HRQoL in patients with moderate-to-severe Crohn ’s disease 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 & AIMS Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α . Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled , double-blind trial . METHODS Ulcerative colitis long-term remission and maintenance with adalimumab 2 ( ULTRA 2 ) was a r and omized , double-blind , placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with moderate-to-severe ulcerative colitis who received concurrent treatment with oral corticosteroids or immunosuppressants . Patients were stratified based on prior exposure to TNF-α antagonists ( either had or had not been previously treated with anti-TNF-α ) and r and omly assigned to groups given adalimumab 160 mg at week 0 , 80 mg at week 2 , and then 40 mg every other week or placebo . Primary end points were remission at weeks 8 and 52 . RESULTS Overall rates of clinical remission at week 8 were 16.5 % on adalimumab and 9.3 % on placebo ( P = .019 ) ; corresponding values for week 52 were 17.3 % and 8.5 % ( P = .004 ) . Among anti-TNF-α naïve patients , rates of remission at week 8 were 21.3 % on adalimumab and 11 % on placebo ( P = .017 ) ; corresponding values for week 52 were 22 % and 12.4 % ( P = .029 ) . Among patients who had previously received anti-TNF agents , rates of remission at week 8 were 9.2 % on adalimumab and 6.9 % on placebo ( P = .559 ) ; corresponding values for week 52 were 10.2 % and 3 % ( P = .039 ) . Serious adverse events occurred in 12 % of patients given adalimumab or placebo . Serious infections developed in 1.6 % of patients given adalimumab and 1.9 % given placebo . In the group given adalimumab , 1 patient developed squamous cell carcinoma and 1 developed gastric cancer . CONCLUSIONS Adalimumab was safe and more effective than placebo in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis who did not have an adequate response to conventional therapy with steroids or immunosuppressants BACKGROUND In chronic inflammatory conditions such as Crohn 's disease , the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins . METHODS We conducted a double-blind , placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn 's disease . Patients were r and omly assigned to receive one of four treatments : two infusions of placebo ; one infusion of 3 mg of natalizumab per kilogram of body weight , followed by placebo ; two infusions of 3 mg of natalizumab per kilogram ; or two infusions of 6 mg of natalizumab per kilogram . Infusions were given four weeks apart . Outcomes included changes in scores for the Crohn 's Disease Activity Index ( higher scores indicate more severe disease ) , the health-related quality of life , and C-reactive protein levels . RESULTS The group given two infusions of 6 mg of natalizumab per kilogram did not have a significantly higher rate of clinical remission ( defined by a score of less than 150 on the Crohn 's Disease Activity Index ) than the placebo group at week 6 ( the prospect ively defined primary end point in the efficacy analysis ) . However , both groups that received two infusions of natalizumab had higher remission rates than the placebo group at multiple time points . Natalizumab also produced a significant improvement in response rates ( defined by a reduction of at least 70 points in the score on the Crohn 's Disease Activity Index ) . The highest remission rate was 44 percent and the highest response rate was 71 percent ( at week 6 in the group given two infusions of 3 mg per kilogram ) . Overall , the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per kilogram had similar effects . The quality of life improved in all natalizumab groups ; C-reactive protein levels improved in groups receiving two infusions of natalizumab . The rates of adverse events were similar in all four groups . CONCLUSIONS Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response , improved the quality of life and C-reactive protein levels , and was well tolerated in patients with active Crohn 's disease BACKGROUND AND AIMS Current treatments for Japanese patients with active Crohn 's disease have not proved optimal , and new treatment options are required . The present study therefore evaluated the efficacy and tolerability of oral budesonide in Japanese patients with mild-to-moderate active Crohn 's disease . METHODS In this multicentre , double-blind , r and omized , parallel-group , Phase II study , patients ( 18 - 65 years ) with baseline Crohn 's Disease Activity Index ( CDAI ) score≥200 were r and omized to once-daily ( od ) oral budesonide 9 mg or 15 mg , or matching placebo , for 8 weeks . Concomitant therapy with sulfasalazine or 5-aminosalicylic acid , and nutritional therapy , was allowed . The rate of remission ( defined as CDAI score≤150 ) after 8 weeks ' treatment ( primary variable ) , health-related quality of life ( assessed using the Inflammatory Bowel Disease Question naire [ IBDQ ] ) , and tolerability were assessed . RESULTS 77 patients were r and omized and 63 completed the study .  The proportion of budesonide-treated patients with remission after 8 weeks ' treatment was higher compared with placebo ( 23.1 % , 28.0 % , and 11.5 % for budesonide 9 mg , 15 mg , and placebo , respectively ; no significant difference ) . The mean change from baseline to week 8 in CDAI total score ( -48.0 , -58.2 , and -27.2 , respectively ) and IBDQ total score ( 10.8 , 23.2 , and 6.5 , respectively ) was greater for budesonide-treated patients than placebo recipients . While budesonide 9 mg and 15 mg demonstrated similar efficacy , budesonide 9 mg caused fewer drug- and glucocorticosteroid-related adverse events and less adrenal suppression . CONCLUSIONS Oral budesonide 9 mg od ( for up to 8 weeks ) may offer a new treatment option for Japanese patients with mild-to-moderate active Crohn 's disease OBJECTIVES : To compare outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with reinitiation of adalimumab ( in the event of clinical deterioration ) for patients with moderate-to-severe Crohn 's disease ( CD ) who participated in the Crohn 's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance ( CHARM ) . METHODS : In the CHARM trial , all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2 , respectively . In total , 778 patients were r and omized at week 4 to one of three groups : ( 1 ) placebo after initial induction doses ( followed by reinitiation of adalimumab therapy ) ; ( 2 ) continuous maintenance treatment with adalimumab 40 mg every other week ( e.o.w . ) ; and ( 3 ) continuous maintenance treatment with adalimumab 40 mg every week . At/after week 12 , patients receiving placebo with flare or non-response could reinitiate open-label adalimumab 40 mg e.o.w . , and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w . Patients in all groups could switch to weekly therapy with continued flare/non-response . In the previously published primary analysis , results for only those patients who had responded at week 4 ( decrease in Crohn 's Disease Activity Index ( CDAI ) of ≥70 points , referred to as “ r and omized responders ” ) and remained on blinded therapy were analyzed . In this analysis , data from all r and omized patients were analyzed based on original r and omized treatment using an intention-to-treat analysis , regardless of whether they subsequently switched to open-label therapy . Disease activity , clinical remission , number of flares , Inflammatory Bowel Disease Question naire ( IBDQ ) score , number of CD-related surgeries , and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups . RESULTS : Results for all outcome measures were superior for both continuous groups compared with the induction only/reinitiation group . On the basis of median CDAI and IBDQ results , patients in both continuous treatment groups achieved statistically significantly greater improvements vs. the induction only/reinitiation group ( P<0.05 ) . At week 56 , a significantly greater percentage of patients who had received continuous adalimumab ( 51 % for e.o.w . and 49 % for weekly ) were in clinical remission vs. the induction only/reinitiation group ( 38 % , P<0.05 ) . Continuous adalimumab therapy was also associated with fewer flares and fewer CD-related surgeries ( P<0.05 ) . Patients in both continuous adalimumab groups had significantly lower risks of CD-related and all-cause hospitalizations than did patients in the induction only/reinitiation group ( P<0.05 ) . CONCLUSIONS : For patients with active CD , continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by reinitiation of adalimumab with clinical deterioration for maintenance of clinical remission , improved quality -of life outcomes , reduced flares , and a decrease in number of surgeries and risk of hospitalization BACKGROUND Although corticosteroids are highly effective in improving symptoms of Crohn 's disease , they may have substantial toxicity . In some patients , attempts to discontinue corticosteroids are unsuccessful . METHODS We conducted a double-blind , placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn 's disease despite a minimum of three months of prednisone therapy . Patients were r and omly assigned to treatment with intramuscular methotrexate ( 25 mg once weekly ) or placebo for 16 weeks . The patients also received prednisone ( 20 mg once a day ) , which was tapered over 10 weeks unless their condition worsened . The primary outcome measure was clinical remission at the end of the 16-week trial . Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn 's Disease Activity Index . RESULTS A total of 141 patients were r and omly assigned in a 2:1 ratio to  methotrexate ( 94 patients ) or placebo ( 47 patients ) . After 16 weeks , 37 patients ( 39.4 percent ) were in clinical remission in the methotrexate group , as compared with 9 patients ( 19.1 percent ) in the placebo group ( P = 0.025 ; relative risk , 1.95 ; 95 percent confidence interval , 1.09 to 3.48 ) . The patients in the methotrexate group received less  prednisone  overall than those in the placebo group ( P = 0.026 ) . The mean ( + /- SE ) score on the Crohn 's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group ( 162 + /- 12 ) than in the placebo group ( 204 + /- 17 , P = 0.002 ) . The changes in quality -of-life scores and serum orosomucoid concentrations were similar . In the methotrexate group , 16 patients ( 17 percent ) withdrew from treatment because of adverse events ( including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6 ) , as compared with 1 patient ( 2 percent ) in the placebo group . CONCLUSIONS In a group of patients with chronically active Crohn 's disease , methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone Background : The safety and efficacy of fontolizumab , a humanized anti‐interferon gamma antibody , was investigated in patients with Crohn 's disease ( CD ) . Elevated gut mucosal levels of interferon gamma , a key cytokine involved in the inflammatory process of CD , are associated with disease symptoms . Methods : A total of 201 patients with Crohn 's Disease Activity Index ( CDAI ) scores between 250 and 450 were r and omized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo , followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks . Clinical response at day 29 , the primary efficacy endpoint , was defined as a decrease in the CDAI of at least 100 points from baseline levels . Results : Of 201 patients , 135 ( 67 % ) completed the study . Day 29 response rates were similar in all treatment groups ( 31%–38 % ) . At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo . All fontolizumab groups had significant improvement in C‐reactive protein levels . The overall frequency of adverse events was similar in all groups ( 58%–75 % ) ; most events were related to exacerbation of CD . There was a low frequency ( 5.2 % ) of neutralizing antibodies to fontolizumab . Conclusions : Although a strong clinical response to fontolizumab was not observed , significant decreases in C‐reactive protein levels suggest a biological effect . Fontolizumab was well tolerated , and further studies to assess its efficacy are warranted . Inflamm Bowel Dis Background : Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis . The benefits of infliximab in Crohn ’s disease are established . We investigated its efficacy in ulcerative colitis . Methods : We conducted a r and omised placebo controlled trial of infliximab ( 5 mg/kg ) in the treatment of glucocorticoid resistant ulcerative colitis . Infusions were given at weeks 0 and 2 . Disease activity and quality of life were recorded over eight weeks of follow up . Remission was defined as an ulcerative colitis symptom score ( UCSS ) of ⩽2 and /or Baron score of 0 at week 6 . Patients not in remission were offered open label infliximab 10 mg/kg and review ed two weeks later . Results : After two weeks , there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 ( 13 % ( 3/23 ) v 5 % ( 1/19 ) ( 95 % confidence interval ( CI ) −9 % to 24 % ) ; p=0.74 ) . After six weeks , remission ( UCSS ⩽2 ) rates were 39 % ( 9/23 ) versus 30 % ( 6/20 ) ( 95 % CI −19 to 34 % ; p=0.76 ) . The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group ( p=0.82 , Mann-Whitney U test ) . A Baron score of 0 was likely in either group ( 26 % ( 6/23 ) v 30 % ( 6/20 ) ( 95 % CI −30 % to 23 % ) ; p=0.96 ) . Improvement in the IBDQ and EuroQol was not significantly different between the groups ( p=0.22 and 0.3 , respectively , Mann-Whitney U test ) . Twenty eligible patients were given open labelled infusions . Remission was achieved in 3/11 ( 27 % ) patients initially treated with infliximab and in 1/9 ( 11 % ) patients treated with placebo . Conclusion : These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis Summary : Our aims were to assess the impact on healthrelated quality of life ( HRQOL ) of a controlled ileal release ( CIR ) formulation of budesonide in active Crohn 's disease ( CD ) and further define the role of HRQOL , using the Inflammatory Bowel Disease Question naire ( IBDQ ) , in assessing outcome in CD . A r and omized trial was conducted in 258 patients with active ileal or ileocecal CD .  Budesonide CIR 1.5 mg , 4.5 mg , 7.5 mg , or placebo was given b.i.d . for 8 weeks . IBDQ score changes were compared among groups . Correlations for IBDQ and Crohn 's Disease Activity Index ( CDAI ) scores were calculated . Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg ( 155 ± 38 ; p = 0.006 ) and 9 mg groups ( 157 ± 33 ; p = 0.0002 ) . Bowel , systemic , social , and emotional subscores were also significantly better ( p < 0.002 ) at 2 and 8 weeks in the 9 mg group . Improved HRQOL scores correlated well with decreased CDAI ( −0.8 < r < −0.4 ) . Average per item change in IBDQ at remission was 1.17 to 1.48 . Prior surgery ( p < 0.005 ) or current smoker ( p < 0.05 ) status predicted poorer initial HRQOL but not response . Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD 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 : Repifermin ( keratinocyte growth factor‐2 ) has been shown to reduce inflammation in animal models of colitis OBJECTIVES : Moderate-to-severe Crohn 's disease ( CD ) is associated with important impairment in health-related quality of life ( HRQOL ) . The aim of this study was to assess the effects of certolizumab pegol ( CZP ) maintenance therapy on HRQOL . METHODS : During an open-label induction phase , study participants with moderate-to-severe CD were treated with 400 mg CZP every other week . Responders were r and omized to monthly maintenance therapy with CZP or placebo . Clinical ly meaningful improvement in HRQOL was evaluated with three patient-reported outcome ( PRO ) instruments . Quality -adjusted life-years ( QALYs ) were calculated from utility scores derived from the EuroQoL-5 dimensions ( EQ-5D ) . Normal life rating was measured by combining clinical disease activity , HRQOL , and measures of professional work productivity and daily activity . RESULTS : A total of 425 responders to induction therapy were r and omized to CZP maintenance ( n=215 ) or placebo ( n=210 ) . Participants assigned to CZP maintenance reported clinical ly meaningful improvements in HRQOL relative to baseline and to placebo-treated participants . More participants receiving treatment with CZP reported clinical ly meaningful improvement in Inflammatory Bowel Disease Question naire ( IBDQ ) score ( 60 vs. 43 % , P<0.001 ) and in Short-Form 36-Item Health Survey ( SF-36 ) physical ( 51 vs. 34 % , P<0.001 ) and mental component summary responses ( 44 vs. 32 % , P=0.016 ) than did those receiving placebo . The proportion of participants who achieved clinical ly meaningful improvement in the EQ-5D plus health status visual analogue scale ( VAS ) was significantly greater in those assigned to CZP maintenance than in those assigned placebo ( 57 vs. 38 % , P<0.001 ) . There was also a significantly greater gain in QALYs for the CZP group as compared with the placebo group ( mean±s.d . 0.25±0.10 and 0.21±0.11 ; P=0.001 ) . Significantly more participants receiving CZP maintenance reported living a normal life ( 21.4 % ) than did those receiving placebo ( 12.9 % , P=0.019 ) . CONCLUSIONS : Maintenance therapy with CZP result ed in statistically significant and clinical ly meaningful improvements in HRQOL , as assessed by multiple PRO instruments . CZP improved and maintained the quality and quantity of the remission and response , as measured by QALYs . Furthermore , a significant proportion of study participants who received CZP  returned to a normal life compared with those who received placebo OBJECTIVES : The ACCENT I study evaluated the long term effects of infliximab as maintenance therapy for patients with Crohn 's disease .  Health-related quality of life ( HRQL ) was also assessed in the trial . METHODS : In ACCENT I , a total of 573 patients received a single infusion of 5 mg/kg infliximab at baseline . After assessment of response at wk 2 , patients were r and omly assigned repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 ( single dose ) , repeat infusions of 5 mg/kg of infliximab at the same time points ( 5 mg/kg maintenance ) , or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg ( 10 mg/kg maintenance ) . HRQL analyses presented include the 335 patients classified as wk-2 responders . The treatment regimens were compared with regard to their change from baseline in the IBDQ and Short Form–36 ( SF-36 ) scores . RESULTS : Baseline scores indicated substantial impairment in HRQL . Throughout the study , all IBDQ and SF-36 scores were improved at all time points compared to baseline . After wk 10 and through wk 54 , these improvements were greater in the two infliximab maintenance groups than in the single-dose group . The mean change from baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group ( 22.1 , p < 0.05 ) and 10-mg/kg maintenance group ( 30.2 , p < 0.001 ) than in the single-dose group ( 8.9 ) . Similarly , the mean change from baseline to wk 54 in the PCS of the SF-36 was greater in the 5-mg/kg maintenance group ( 6.1 , p < 0.05 ) and 10-mg/kg maintenance group ( 7.2 , p < 0.01 ) than in the single-dose group ( 2.5 ) . CONCLUSIONS : Infliximab therapy provides substantially improved HRQL as measured by both the disease-specific IBDQ and the generic SF-36 . A maintenance regimen of either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg infliximab infusion in sustaining this benefit BACKGROUND & AIMS Little is known about the efficacy of golimumab , a fully human monoclonal antibody to tumor necrosis factor ( TNF ) -α , for treatment of ulcerative colitis ( UC ) . We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment . METHODS We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC ( Mayo score : 6 - 12 ; endoscopic subscore ≥ 2 ; 774 patients in phase 3 ) . Patients were r and omly assigned to groups given golimumab doses of 100 mg and then 50 mg ( phase 2 only ) , 200 mg and then 100 mg , or 400 mg and then 200 mg , 2 weeks apart . The phase 3 primary end point was week-6 clinical response . Secondary end points included week-6 clinical remission , mucosal healing , and Inflammatory Bowel Disease Question naire ( IBDQ ) score change . RESULTS In phase 2 , median changes from baseline in the Mayo score were -1.0 , -3.0 , -2.0 , and -3.0 , in the groups given placebo , 100 mg/50 mg , 200/100 mg , and 400/200 mg golimumab , respectively . In phase 3 , rates of clinical response at week 6 were 51.0 % and 54.9 % among patients given 200 mg/100 mg and 400 mg/200 mg golimumab , respectively , vs 30.3 % among those given placebo ( both , P ≤ .0001 ) . Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group ( P ≤ .0014 , all comparisons ) . Rates of serious adverse events were 6.1 % and 3.0 % , and rates of serious infection were 1.8 % and 0.5 % , in the placebo and golimumab groups , respectively . One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess . CONCLUSIONS Treatment with subcutaneous golimumab induces clinical response , remission , and mucosal healing , and increases quality of life in larger percentages of patients with active UC than placebo . Clinical Trials.gov Number : NCT00487539
Background and Aims Placebo effect in health-related quality of life [ HRQoL ] of inflammatory bowel disease [ IBD ] patients has been poorly characterised .
This systematic review and meta- analysis aim ed to assess : i ] mean improvements in IBDQ [ Inflammatory Bowel Disease Question naire ] and SF-36 [ 36-Item Short Form Health Survey ] scores among placebo-treated IBD patients ; and ii ] the proportion of  placebo-treated patients achieving IBDQ-defined response and remission and correspondent odds ratios [ OR ] .