crohn s disease is a chronic relapsing and remitting , inflammatory bowel disease ( ibd ) that has a significant impact on health - related quality of life ( hrqol ) [ 1 , 2 ] . hrqol has been recognized as an important health outcome and has been defined in the medical setting as  a concept encompassing a broad range of physical and psychological characteristics and limitations which describe an individual s ability to function and derive satisfaction from doing so  . crohn s disease frequently begins in early adulthood , causing a heavy disease burden in a relatively young patient population . consequently , many patients will be affected for most of their adult life . in crohn s disease , health status is affected as much by psychosocial factors and functional status as by disease activity . for example , the need to wear an ostomy bag may adversely affect self - image , and this has been reported to be a common worry for patients with crohn s disease . moreover , previous studies have demonstrated a high correlation between disease severity , as measured by the crohn s disease activity index ( cdai ) , and hrqol , as assessed using the inflammatory bowel disease questionnaire ( ibdq ) [ 7 , 8 ] . a large longitudinal study prospectively assessed the hrqol of patients with crohn s disease over 1  year and determined influencing factors . the following factors were associated with a negative impact on overall hrqol : female gender , tobacco use , active crohn s disease , involvement of the colon , hospitalization , corticosteroid treatment , and surgery in the past 3  months ( order does not indicate priority ) . these findings were reflected in a survey of patients with a long - term diagnosis of crohn s disease . it is therefore important to include improvement in hrqol as a key therapeutic goal in the treatment of patients with crohn s disease . conventional treatment options for crohn s disease include aminosalicylates , antibiotics , corticosteroids , immunomodulators , and surgery . however , in some patients , the disease can be refractory or unresponsive to certain pharmacologic treatments . furthermore , corticosteroids are associated with a risk of dependency and potentially serious side effects ( e.g. , diabetes , osteoporosis , moon face , and acne ) , which are detrimental to a patient s hrqol and may negatively affect self - esteem [ 1113 ] . such treatments therefore require careful management . additionally , it is rarely possible to achieve long - term relief from crohn s disease with a single surgical procedure , and as a result , patients with crohn s disease fear surgery so much that their hrqol is reduced . it is now well accepted that tumor necrosis factor  ( tnf ) plays a pivotal role in the underlying inflammatory pathophysiology of crohn s disease . furthermore , neutralization of tnf has been shown to improve the symptoms of this debilitating illness [ 13 , 16 ] . infliximab has been shown to improve hrqol , as measured by the ibdq and the short - form health survey ( sf-36 ) [ 8 , 17 ] , but the occurrence of infusion reactions along with the risk of developing anti - infliximab antibodies , which can reduce long - term efficacy , could negatively impact hrqol over time . patients may feel that subcutaneous treatment has advantages over treatments requiring infusion ; a long stay at the clinic may negatively impact a patient s daily life . this increased freedom in patient treatment management may lead to improved treatment compliance with a consequent impact on therapeutic outcomes . thus , there is a need for alternative long - term therapies for moderate - to - severe crohn s disease that have minimal negative impact on patients everyday life while also reducing the impact of the disease on patients hrqol . certolizumab pegol is the first polyethylene glycolated ( pegylated ) anti - tnf antibody fragment ( fab ) to be studied in crohn s disease . unlike conventional anti - tnf agents , certolizumab pegol lacks the crystallizable fragment ( fc ) region , thus potentially avoiding unwanted effects . certolizumab pegol is administered by subcutaneous injection once every 4  weeks ( more frequent dosing may be used during an induction phase ) . certolizumab pegol 400  mg administered subcutaneously demonstrated efficacy and was well tolerated in patients with moderate - to - severe active crohn s disease in phases ii   and iii ( precise 1 and precise 2 [ 22 , 23 ] ) studies . certolizumab pegol has also demonstrated clinical efficacy and good tolerability in patients with rheumatoid arthritis [ 24 , 25 ] . this is the first paper to report the effect of certolizumab pegol , a monthly subcutaneous treatment , on the hrqol of patients with moderate - to - severe active crohn s disease in a phase ii placebo - controlled study . this study was approved by the independent ethics committee / institutional review board for each center before initiation . it was conducted in accordance with the international conference for harmonization guidelines for good clinical practice and the declaration of helsinki ( revised 1996 ) . written informed consent was obtained from each patient at screening before any study procedures were performed . adult patients ( age 18  years ) with moderate - to - severe active crohn s disease , as defined by a cdai score of 220450 points during the week before the administration of the first dose of study drug , were eligible for the study . exclusion criteria included suspected or diagnosed abscess , a bowel perforation or evidence of non - inflammatory obstruction in 6  months before screening , extensive bowel resection , a functional colostomy or ileostomy , or a known history of tuberculosis . concomitant medication was allowed , provided that doses were stable and could be continued for the 12-week double - blind period and the 8-week follow - up . this was a multicenter , randomized , double - blind , placebo - controlled , 12-week study conducted at 58 international centers between february 2001 and march 2002 . an 8-week follow - up period allowed collection of additional safety data . at screening , patients with moderate - to - severe active crohn s disease were stratified according to concomitant steroids , immunosuppressants , or long - term anti - infectives . eligible patients were randomized ( 1:1:1:1 ) to receive certolizumab pegol ( 100 , 200 , or 400  mg ) or placebo ( 0.9% w / v saline ) by subcutaneous injection at weeks 0 , 4 , and 8 ( fig .  1 ) . before dosing , patients demography , medical history , and concomitant diseases were recorded . 1study design ( showing the total numbers of patients recruited into each treatment group ) study design ( showing the total numbers of patients recruited into each treatment group ) the primary endpoint of the study was the proportion of patients achieving a clinical response [ 100-point decrease in cdai score or cdai score 150 points ( remission ) ] at week 12 . hrqol was a secondary endpoint evaluated at baseline ( week  0 , pre - injection ) and at weeks  2 , 4 , 6 , 8 , 10 , and 12 using the 32-item self - administered ibdq . the questionnaire assesses the four aspects of a patient s life that are affected by ibd : symptoms directly related to the primary bowel symptoms , systemic symptoms , emotional function , and social function . the reliability , validity , and responsiveness of the ibdq have been demonstrated by guyatt et al . [ 26 , 27 ] and irvine et al . [ 7 , 28 ] . total ibdq scores range from 32 to 224 , with a higher score indicating better hrqol . remission is generally indicated by a score of at least 170 points , and a change of 16 points is regarded as clinically meaningful . in addition to a total score , domain scores can be calculated for the bowel symptoms , systemic symptoms , emotional function , and social function domains . ibdq measurements were performed in parallel with determination of cdai score and serum concentrations of c - reactive protein ( crp ) . official ibdq versions translated into danish , french , german , and swedish were used . our own translations were used for russian , serbian , and afrikaans . to assess whether our own translated versions of the ibdq provided a valid measure of hrqol , we compared scores of the translated versions with those of the official translated versions and evaluated those scores in relation to the patient s cdai scores . a sensitivity analysis was also carried out to check for influence of specific item scores on the resulting total scores . the results of these analyses demonstrated that our own translated versions of the ibdq provided a valid measure of hrqol , comparable to the official , translated versions . a sample size of 260 patients was calculated to give approximately 83% power to detect a true difference between treatment groups of 23% for the primary endpoint of the study , based on a placebo response rate of 12% . after screening , patients were to be randomized in a 1:1:1:1 ratio ( 65 patients to each of the four treatment groups ) . therefore , 195 patients were to receive certolizumab pegol and 65 were to receive placebo . efficacy was assessed for the intent - to - treat ( itt ) population , which included all patients who received at least one injection and had at least one efficacy measurement after the first injection . patients who terminated the trial prematurely were advanced to the end - of - study visit . relationships between cdai and ibdq global scores at week  12 were assessed for the itt population using kendall s tau coefficient , a measure of the strength of dependence showing to what extent these two variables move in the same direction . changes from baseline in ibdq total score and individual domain scores for each treatment group were formally compared with the placebo group . least - squares means , adjusted for stratum , pooled country , and baseline ibdq score , were compared across treatment groups . fisher s exact test was used to compare the proportion of patients who achieved remission ( defined as an ibdq total score of 170 points ) in each active treatment group with that for the placebo group at each week . the analyses were performed based on both the overall itt population and in the subgroup of patients with elevated baseline crp ( 10  mg this study was approved by the independent ethics committee / institutional review board for each center before initiation . it was conducted in accordance with the international conference for harmonization guidelines for good clinical practice and the declaration of helsinki ( revised 1996 ) . written informed consent was obtained from each patient at screening before any study procedures were performed . adult patients ( age 18  years ) with moderate - to - severe active crohn s disease , as defined by a cdai score of 220450 points during the week before the administration of the first dose of study drug , were eligible for the study . exclusion criteria included suspected or diagnosed abscess , a bowel perforation or evidence of non - inflammatory obstruction in 6  months before screening , extensive bowel resection , a functional colostomy or ileostomy , or a known history of tuberculosis . concomitant medication was allowed , provided that doses were stable and could be continued for the 12-week double - blind period and the 8-week follow - up . this was a multicenter , randomized , double - blind , placebo - controlled , 12-week study conducted at 58 international centers between february 2001 and march 2002 . an 8-week follow - up period allowed collection of additional safety data . at screening , patients with moderate - to - severe active crohn s disease were stratified according to concomitant steroids , immunosuppressants , or long - term anti - infectives . eligible patients were randomized ( 1:1:1:1 ) to receive certolizumab pegol ( 100 , 200 , or 400  mg ) or placebo ( 0.9% w / v saline ) by subcutaneous injection at weeks 0 , 4 , and 8 ( fig .  1 ) . before dosing , 1study design ( showing the total numbers of patients recruited into each treatment group ) study design ( showing the total numbers of patients recruited into each treatment group ) the primary endpoint of the study was the proportion of patients achieving a clinical response [ 100-point decrease in cdai score or cdai score 150 points ( remission ) ] at week 12 . hrqol was a secondary endpoint evaluated at baseline ( week  0 , pre - injection ) and at weeks  2 , 4 , 6 , 8 , 10 , and 12 using the 32-item self - administered ibdq . the questionnaire assesses the four aspects of a patient s life that are affected by ibd : symptoms directly related to the primary bowel symptoms , systemic symptoms , emotional function , and social function . the reliability , validity , and responsiveness of the ibdq have been demonstrated by guyatt et al . [ 26 , 27 ] and irvine et al . [ 7 , 28 ] . total ibdq scores range from 32 to 224 , with a higher score indicating better hrqol . remission is generally indicated by a score of at least 170 points , and a change of 16 points is regarded as clinically meaningful . in addition to a total score , domain scores can be calculated for the bowel symptoms , systemic symptoms , emotional function , and social function domains . ibdq measurements were performed in parallel with determination of cdai score and serum concentrations of c - reactive protein ( crp ) . official ibdq versions translated into danish , french , german , and swedish were used . our own translations were used for russian , serbian , and afrikaans . to assess whether our own translated versions of the ibdq provided a valid measure of hrqol , we compared scores of the translated versions with those of the official translated versions and evaluated those scores in relation to the patient s cdai scores . a sensitivity analysis was also carried out to check for influence of specific item scores on the resulting total scores . the results of these analyses demonstrated that our own translated versions of the ibdq provided a valid measure of hrqol , comparable to the official , translated versions . a sample size of 260 patients was calculated to give approximately 83% power to detect a true difference between treatment groups of 23% for the primary endpoint of the study , based on a placebo response rate of 12% . after screening , patients were to be randomized in a 1:1:1:1 ratio ( 65 patients to each of the four treatment groups ) . therefore , 195 patients were to receive certolizumab pegol and 65 were to receive placebo . efficacy was assessed for the intent - to - treat ( itt ) population , which included all patients who received at least one injection and had at least one efficacy measurement after the first injection . patients who terminated the trial prematurely were advanced to the end - of - study visit . relationships between cdai and ibdq global scores at week  12 were assessed for the itt population using kendall s tau coefficient , a measure of the strength of dependence showing to what extent these two variables move in the same direction . changes from baseline in ibdq total score and individual domain scores for each treatment group were formally compared with the placebo group . least - squares means , adjusted for stratum , pooled country , and baseline ibdq score , were compared across treatment groups . fisher s exact test was used to compare the proportion of patients who achieved remission ( defined as an ibdq total score of 170 points ) in each active treatment group with that for the placebo group at each week . the analyses were performed based on both the overall itt population and in the subgroup of patients with elevated baseline crp ( 10  mg the clinical efficacy and safety assessments of this phase ii dose - finding study have been reported in detail elsewhere . because the 400  mg dose was identified as being the most appropriate dose , this paper focuses on data for patients receiving certolizumab pegol 400  mg . in total , 372 patients were screened of whom 292 patients were enrolled ( cdai score < 220 points was the most common reason for screening failure ) . of these 292 patients , 291 were included in the itt population used to measure the efficacy endpoints according to cdai scores [ 1 patient ( 400  mg group ) was excluded because of missing efficacy data ] . baseline ibdq scores were not obtained for one patient in the certolizumab pegol 100  mg treatment group . seventy - five patients ( 25.7% ) withdrew from the study by week  12 . baseline crp measurements were obtained for 290 of the 291 patients in the itt population . elevated baseline crp levels ( 10  mg one of these patients was the patient in the certolizumab pegol 100  mg treatment group who was excluded from analyses as a result of baseline ibdq scores not being obtained . the subgroup analyses of ibdq by baseline crp status were therefore performed on data from 118 patients with an elevated baseline crp concentration . the four treatment groups were generally well matched in terms of demographic and clinical characteristics ( including baseline ibdq total score and concomitant medication profile ; table  1 ) . in the itt population , 21.6% of patients had received previous anti - tnf therapy , and 15.5% had concomitant medication with both immunomodulators and steroids . table  1baseline demographic and clinical characteristics ( intent to treat population used to measure efficacy endpoints according to crohn s disease activity index scores )  placebo(n  =  73)certolizumab pegol100  mg ( n  =  74)200  mg ( n  =  72)400  mg ( n  =  72)mean cdai score ( range)291.5 ( 206448)299.2 ( 194520)310.7 ( 184446)304.5 ( 204461)mean ibdq score ( range)122.9 ( 61190)132.2 ( 66189)122.9 ( 74189)126.5 ( 71177)geometric mean plasma crp , mg / l ( range)7.268 ( 0.2786.10)6.231 ( 0.15141.00)6.475 ( 0.17127.00)7.738 ( 0.35128.28)crp    10  mg / l , n ( % ) 28 ( 38.4)31 ( 42.5)28 ( 38.9)32 ( 44.4)concomitant medications , n ( % )  aminosalicylates29 ( 39.7)37 ( 50.0)32 ( 44.4)28 ( 38.9 )  anti - infectives7 ( 9.6)6 ( 8.1)7 ( 9.7)6 ( 8.3 )  antidiarrheals10 ( 13.7)19 ( 25.7)16 ( 22.2)12 ( 16.7 )  steroids29 ( 39.7)24 ( 32.4)29 ( 40.3)22 ( 30.6 )  codeine and derivatives6 ( 8.2)5 ( 6.8)5 ( 6.9)2 ( 2.8)immunomodulators  azathioprine17 ( 23.3)13 ( 17.6)23 ( 31.9)22 ( 30.6 )  6-mercaptopurine4 ( 5.5)9 ( 12.2)2 ( 2.8)2 ( 2.8 )  methotrexate5 ( 6.8)4 ( 5.4)4 ( 5.6)3 ( 4.2)cdai crohn s disease activity index ; crp c - reactive protein ; ibdq inflammatory bowel disease questionnaire ; n number of patientsmaximum score is 224 points.data missing for one patient . baseline demographic and clinical characteristics ( intent to treat population used to measure efficacy endpoints according to crohn s disease activity index scores ) cdai crohn s disease activity index ; crp c - reactive protein ; ibdq inflammatory bowel disease questionnaire ; n number of patients maximum score is 224 points . the onset of effect ( clinical response ) of certolizumab pegol was evident at week  2 , when certolizumab pegol treatment produced a statistically significant improvement in cdai score compared with placebo ( certolizumab pegol 400  mg 33.3% vs placebo 15.1% ; p  =  0.010 ) . clinical response rates were highest in the certolizumab pegol 400  mg group at all time points , with maximal response at week  10 ( certolizumab pegol 400  mg 52.8% vs placebo 30.1% ; p  =  0.006 ) . lower cdai score ( representing lower disease severity ) was associated with a higher ibdq global score ( representing better hrqol ) , as reflected by a high negative kendall s tau value ( 0.48 ; p  < patients demonstrated hrqol improvements from baseline , as measured by change in ibdq total score , by the first assessment point , week  2 [ certolizumab pegol 100  mg , 16.6 points ; certolizumab pegol 200  mg , 21.8 points ( p    0.05 vs placebo ) ; certolizumab pegol 400  mg , 22.8 points ( p    0.05 vs placebo ) ; placebo , 10.6 points ] ( fig .  2 ) . patients receiving certolizumab pegol 400  mg experienced statistically significantly greater improvements from baseline in ibdq total score at all time points ( p    0.05 ) compared with those receiving placebo . the greatest increase in ibdq total score was recorded at week  10 ( certolizumab pegol 400  mg 32.2 points vs 18.6 points for placebo ; p    0.05 ) . approximately half of the patients treated with certolizumab pegol 400  mg demonstrated clinically meaningful improvements in ibdq total score ( 16-point increase ) at week  2 ( 52.8% ) and at week  12 ( 66.7% ) . 2mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) total score during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) total score during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) as early as week  2 , patients receiving certolizumab pegol 400  mg demonstrated statistically significant improvements in the bowel symptoms and emotional function domains of the ibdq relative to placebo ( fig .  3 ) . improvement in the systemic symptoms domain score approached statistical significance at week  2 ( p  =  0.054 ) . interestingly , patients in the certolizumab pegol 200  mg group achieved statistically significantly greater improvements than those receiving placebo in ibdq total score and all four ibdq domains at week  2 ( figs .  2 and 3a  d ) . 3mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) domain scores during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) : a bowel symptoms domain , b systemic symptoms domain , c emotional function domain , and d social function domain mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) domain scores during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) : a bowel symptoms domain , b systemic symptoms domain , c emotional function domain , and d social function domain emotional function and systemic symptoms were the domains that patients reported as being most improved by certolizumab pegol treatment . at every assessment , patients receiving certolizumab pegol 400  mg showed statistically significantly ( p    0.05 ) greater improvements in emotional function domain scores than those receiving placebo ( fig .  3c ) . they also demonstrated statistically significantly greater improvements in systemic symptoms domain scores than those receiving placebo at weeks  4 , 8 , 10 , and 12 ( fig . the improvements patients experienced in social function domain scores approached statistical significance ( p  =  0.054 ) at week  4 ( fig . the remission rate in the certolizumab pegol 400  mg group was highest at week  10 . this was statistically significantly greater than in the placebo group ( table  2 ) . the proportion of patients achieving remission in the certolizumab pegol 400  mg group was also statistically significantly greater than in the placebo group at weeks  6 , 8 , and 12 . the subgroup of patients with elevated crp showed similar improvements in ibdq scores to those observed in the itt population . table  2proportion of patients achieving remission defined by inflammatory bowel disease questionnaire total score ( 170 points)patients ( % ) , intent - to - treat population ( n  =  290)weekplacebo ( n  =  73)certolizumab pegol100  mg ( n  =  73)200  mg ( n  =  72)400  mg ( n  =  72)217.832.919.427.8419.237.0 * 26.433.3617.835.6 * 30.638.9 * 821.935.629.238.9 * 1027.443.836.147.2 * 1223.338.423.638.9*the higher remission rate at week  2 in the certolizumab pegol 100  mg group compared with higher - dose groups may reflect the slightly higher mean inflammatory bowel disease questionnaire ( ibdq ) score at baseline in this group . however , certolizumab pegol 400  mg resulted in the greatest mean change in ibdq at all time points.*p 0.05 vs placebo proportion of patients achieving remission defined by inflammatory bowel disease questionnaire total score ( 170 points ) the higher remission rate at week  2 in the certolizumab pegol 100  mg group compared with higher - dose groups may reflect the slightly higher mean inflammatory bowel disease questionnaire ( ibdq ) score at baseline in this group . however , certolizumab pegol 400  mg resulted in the greatest mean change in ibdq at all time points . in total , 372 patients were screened of whom 292 patients were enrolled ( cdai score < 220 points was the most common reason for screening failure ) . of these 292 patients , 291 were included in the itt population used to measure the efficacy endpoints according to cdai scores [ 1 patient ( 400  mg group ) was excluded because of missing efficacy data ] . baseline ibdq scores were not obtained for one patient in the certolizumab pegol 100  mg treatment group . seventy - five patients ( 25.7% ) withdrew from the study by week  12 . baseline crp measurements were obtained for 290 of the 291 patients in the itt population . elevated baseline crp levels ( 10  mg one of these patients was the patient in the certolizumab pegol 100  mg treatment group who was excluded from analyses as a result of baseline ibdq scores not being obtained . the subgroup analyses of ibdq by baseline crp status were therefore performed on data from 118 patients with an elevated baseline crp concentration . the four treatment groups were generally well matched in terms of demographic and clinical characteristics ( including baseline ibdq total score and concomitant medication profile ; table  1 ) . in the itt population , 21.6% of patients had received previous anti - tnf therapy , and 15.5% had concomitant medication with both immunomodulators and steroids . table  1baseline demographic and clinical characteristics ( intent to treat population used to measure efficacy endpoints according to crohn s disease activity index scores )  placebo(n  =  73)certolizumab pegol100  mg ( n  =  74)200  mg ( n  =  72)400  mg ( n  =  72)mean cdai score ( range)291.5 ( 206448)299.2 ( 194520)310.7 ( 184446)304.5 ( 204461)mean ibdq score ( range)122.9 ( 61190)132.2 ( 66189)122.9 ( 74189)126.5 ( 71177)geometric mean plasma crp , mg / l ( range)7.268 ( 0.2786.10)6.231 ( 0.15141.00)6.475 ( 0.17127.00)7.738 ( 0.35128.28)crp    10  mg / l , n ( % ) 28 ( 38.4)31 ( 42.5)28 ( 38.9)32 ( 44.4)concomitant medications , n ( % )  aminosalicylates29 ( 39.7)37 ( 50.0)32 ( 44.4)28 ( 38.9 )  anti - infectives7 ( 9.6)6 ( 8.1)7 ( 9.7)6 ( 8.3 )  antidiarrheals10 ( 13.7)19 ( 25.7)16 ( 22.2)12 ( 16.7 )  steroids29 ( 39.7)24 ( 32.4)29 ( 40.3)22 ( 30.6 )  codeine and derivatives6 ( 8.2)5 ( 6.8)5 ( 6.9)2 ( 2.8)immunomodulators  azathioprine17 ( 23.3)13 ( 17.6)23 ( 31.9)22 ( 30.6 )  6-mercaptopurine4 ( 5.5)9 ( 12.2)2 ( 2.8)2 ( 2.8 )  methotrexate5 ( 6.8)4 ( 5.4)4 ( 5.6)3 ( 4.2)cdai crohn s disease activity index ; crp c - reactive protein ; ibdq inflammatory bowel disease questionnaire ; n number of patientsmaximum score is 224 points.data missing for one patient . baseline demographic and clinical characteristics ( intent to treat population used to measure efficacy endpoints according to crohn s disease activity index scores ) cdai crohn s disease activity index ; crp c - reactive protein ; ibdq inflammatory bowel disease questionnaire ; n number of patients maximum score is 224 points . the onset of effect ( clinical response ) of certolizumab pegol was evident at week  2 , when certolizumab pegol treatment produced a statistically significant improvement in cdai score compared with placebo ( certolizumab pegol 400  mg 33.3% vs placebo 15.1% ; p  =  0.010 ) . clinical response rates were highest in the certolizumab pegol 400  mg group at all time points , with maximal response at week  10 ( certolizumab pegol 400  mg 52.8% vs placebo 30.1% ; p  =  0.006 ) . lower cdai score ( representing lower disease severity ) was associated with a higher ibdq global score ( representing better hrqol ) , as reflected by a high negative kendall s tau value ( 0.48 ; p  < patients demonstrated hrqol improvements from baseline , as measured by change in ibdq total score , by the first assessment point , week  2 [ certolizumab pegol 100  mg , 16.6 points ; certolizumab pegol 200  mg , 21.8 points ( p    0.05 vs placebo ) ; certolizumab pegol 400  mg , 22.8 points ( p    0.05 vs placebo ) ; placebo , 10.6 points ] ( fig .  2 ) . patients receiving certolizumab pegol 400  mg experienced statistically significantly greater improvements from baseline in ibdq total score at all time points ( p    0.05 ) compared with those receiving placebo . the greatest increase in ibdq total score was recorded at week  10 ( certolizumab pegol 400  mg 32.2 points vs 18.6 points for placebo ; p    0.05 ) . approximately half of the patients treated with certolizumab pegol 400  mg demonstrated clinically meaningful improvements in ibdq total score ( 16-point increase ) at week  2 ( 52.8% ) and at week  12 ( 66.7% ) . 2mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) total score during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) total score during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) as early as week  2 , patients receiving certolizumab pegol 400  mg demonstrated statistically significant improvements in the bowel symptoms and emotional function domains of the ibdq relative to placebo ( fig .  3 ) . improvement in the systemic symptoms domain score approached statistical significance at week  2 ( p  =  0.054 ) . interestingly , patients in the certolizumab pegol 200  mg group achieved statistically significantly greater improvements than those receiving placebo in ibdq total score and all four ibdq domains at week  2 ( figs . 3mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) domain scores during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) : a bowel symptoms domain , b systemic symptoms domain , c emotional function domain , and d social function domain mean change from baseline in inflammatory bowel disease questionnaire ( ibdq ) domain scores during 12  weeks subcutaneous treatment with either certolizumab pegol or placebo in patients with moderate - to - severe crohn s disease ( intent - to - treat population ) ; least - squares means ( adjusted for stratum , pooled country , and baseline score ) : a bowel symptoms domain , b systemic symptoms domain , c emotional function domain , and d social function domain emotional function and systemic symptoms were the domains that patients reported as being most improved by certolizumab pegol treatment . at every assessment , patients receiving certolizumab pegol 400  mg showed statistically significantly ( p    0.05 ) greater improvements in emotional function domain scores than those receiving placebo ( fig .  3c ) . they also demonstrated statistically significantly greater improvements in systemic symptoms domain scores than those receiving placebo at weeks  4 , 8 , 10 , and 12 ( fig . the improvements patients experienced in social function domain scores approached statistical significance ( p  =  0.054 ) at week  4 ( fig . the remission rate in the certolizumab pegol 400  mg group was highest at week  10 . this was statistically significantly greater than in the placebo group ( table  2 ) . the proportion of patients achieving remission in the certolizumab pegol 400  mg group was also statistically significantly greater than in the placebo group at weeks  6 , 8 , and 12 . the subgroup of patients with elevated crp showed similar improvements in ibdq scores to those observed in the itt population . table  2proportion of patients achieving remission defined by inflammatory bowel disease questionnaire total score ( 170 points)patients ( % ) , intent - to - treat population ( n  =  290)weekplacebo ( n  =  73)certolizumab pegol100  mg ( n  =  73)200  mg ( n  =  72)400  mg ( n  =  72)217.832.919.427.8419.237.0 * 26.433.3617.835.6 * 30.638.9 * 821.935.629.238.9 * 1027.443.836.147.2 * 1223.338.423.638.9*the higher remission rate at week  2 in the certolizumab pegol 100  mg group compared with higher - dose groups may reflect the slightly higher mean inflammatory bowel disease questionnaire ( ibdq ) score at baseline in this group . however , certolizumab pegol 400  mg resulted in the greatest mean change in ibdq at all time points.*p 0.05 vs placebo proportion of patients achieving remission defined by inflammatory bowel disease questionnaire total score ( 170 points ) the higher remission rate at week  2 in the certolizumab pegol 100  mg group compared with higher - dose groups may reflect the slightly higher mean inflammatory bowel disease questionnaire ( ibdq ) score at baseline in this group . however , certolizumab pegol 400  mg resulted in the greatest mean change in ibdq at all time points . patients with crohn s disease often have poor hrqol , with disease - related concerns , such as worry about needing surgery , being the main causal factor . it therefore follows that treatments relieving the symptoms of crohn s disease and/or reducing the risk of surgery should improve hrqol in patients with crohn s disease . certolizumab pegol administered subcutaneously every 4  weeks is a rapid and clinically effective treatment of moderate - to - severe crohn s disease with the 400  mg dose ( highest dose tested ) inducing the highest response rates [ 21 , 22 , 23 ] . certolizumab pegol 400  mg appears to exert a rapid , consistently positive effect on hrqol in patients with moderate - to - severe crohn s disease . patients who received certolizumab pegol 400  mg demonstrated statistically significantly greater improvements in ibdq total score than those in the placebo group as early as week 2 and at all subsequent time points . as a reflection of the lower baseline ibdq scores in the 400  mg group , patients in this group experienced the greatest improvement , despite the remission rate ( which is the proportion of patients reaching a pre - defined score ) being higher in the 100  mg group . improvements in hrqol were not dependent on baseline crp level . higher baseline crp concentration was associated with greater improvement in clinical variables in this phase ii study , but such a relationship has not been evident in phase iii studies . in addition , patients receiving certolizumab pegol 200  mg showed a statistically significantly greater change from baseline in ibdq total score than those receiving placebo at weeks  2 and 4 . collectively , these findings suggest that certolizumab pegol has an early treatment effect in patients with moderate - to - severe crohn s disease . the benefits of certolizumab pegol on hrqol were also apparent in the phase iii studies [ 22 , 23 , 31 , 32 ] . improvements in emotional well - being ( e.g. depression , anxiety , irritability , and anger resulting from bowel problems ) and systemic symptom domains were particularly marked with certolizumab pegol treatment . it appears that the improvements in these two domains of the ibdq are largely responsible for the reported beneficial effect of certolizumab pegol on hrqol . overall , these findings suggest that certolizumab pegol alleviates the psychological symptoms associated with crohn s disease and improves a patient s general well - being , in addition to providing clinical benefits in terms of cdai response . hrqol provides an integral picture of the interactions between a patient s disease , their treatment , and quality of life  positive effects resulting from the efficacy of a treatment and negative effects caused by adverse events are evaluated . few trials have examined the effects of conventional agents upon hrqol in patients with crohn s disease . while corticosteroids are effective in controlling acute crohn s disease and are reported to improve ibdq scores , the potentially serious adverse events associated with corticosteroids may negate any positive effects on hrqol gained through control of symptoms . additionally , corticosteroids are not suitable for maintenance treatment . improvements in hrqol have been observed with methotrexate treatment in a large , randomized , double - blind , placebo - controlled study . however , 17% of patients ( 16/94 ) receiving methotrexate were withdrawn from the study because of adverse events compared with 2% of placebo - treated patients ( 1/47 ) . the improvements in hrqol observed with certolizumab pegol in this study appear to be similar to those reported in patients with crohn s disease after treatment with infliximab [ 8 , 17 , 35 ] . similarly , natalizumab has been shown to improve hrqol in patients with crohn s disease . given the detrimental effects of crohn s disease on physical and psychosocial functioning , additional research is needed to assess the impact of currently available and newer therapies on hrqol . although hrqol was evaluated using the self - administered ibdq , which has proved to be a valid and reliable disease - specific instrument for determining health status in patients with crohn s disease , the analyses presented in this paper were purely exploratory in nature , and firm conclusions can not be drawn from the results described . however , clinical benefit was also accompanied by improved hrqol in the phase iii studies [ 22 , 23 , 31 , 32 ] . further benefits may be gained through the good tolerability of certolizumab pegol   and convenience of subcutaneous dosing with certolizumab pegol once every 4  weeks . this study demonstrates that the clinical efficacy of certolizumab pegol in patients with moderate - to - severe crohn s disease , which is evident within 2  weeks of injection , is paralleled by improvements in hrqol . the benefits of certolizumab pegol were most pronounced at the highest dose tested ( 400  g ) . improvements in emotional well - being and systemic symptoms appear to be largely responsible for the observed beneficial effect of certolizumab pegol on hrqol .