human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective . One additional treatment may be tofacitinib ( CP-690,550 ) , an oral inhibitor of Janus kinases 1 , 2 , and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 , which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2 , 4 , 7 , 9 , 15 , and 21 . These cytokines are integral to lymphocyte activation , function , and proliferation . METHODS In a double-blind , placebo-controlled , phase 2 trial , we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis . Patients were r and omly assigned to receive tofacitinib at a dose of 0.5 mg , 3 mg , 10 mg , or 15 mg or placebo twice daily for 8 weeks . The primary outcome was a clinical response at 8 weeks , defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity ( possible score , 0 to 12 , with higher scores indicating more severe disease ) of 3 or more and a relative decrease from baseline of 30 % or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 . RESULTS The primary outcome , clinical response at 8 weeks , occurred in 32 % , 48 % , 61 % , and 78 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.39 ) , 3 mg ( P=0.55 ) , 10 mg ( P=0.10 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 42 % of patients receiving placebo . Clinical remission ( defined as a Mayo score ≤2 , with no subscore > 1 ) at 8 weeks occurred in 13 % , 33 % , 48 % , and 41 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.76 ) , 3 mg ( P=0.01 ) , 10 mg ( P<0.001 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 10 % of patients receiving placebo . There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol . Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 . CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00787202 . ) 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 Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis . Here , tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented . Methods Study A3921041 was a multi-centre , open-label , long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate .  Patients received tofacitinib 5 mg twice daily ( BID ) or tofacitinib 10 mg BID . Dose adjustment of tofacitinib during treatment period , and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted . Primary endpoints were adverse events , laboratory parameters and vital signs . Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates , Disease Activity Score (DAS)28 - 4(erythrocyte sedimentation rate (ESR))<2.6 response rate ( DAS-defined remission ) and Health Assessment Question naire-Disability Index ( HAQ-DI ) score . Safety and efficacy data were assessed throughout the study . Results A total of 486 patients were recruited and treated ( 1439.9 patient-years of exposure ) . 308 patients completed the study .  Median ( range ) duration of treatment in this extension study was 1185 ( 5–2016 ) days . 476 patients ( 97.9 % ) experienced adverse events ; the majority of which ( 97.8 % ) were of mild or moderate severity . The two most common treatment-emergent adverse events were nasopharyngitis ( n = 293 , 60.3 % ) and herpes zoster ( n = 94 , 19.3 % ) . For all tofacitinib-treated patients , the incidence rate ( patients with events per 100 patient-years ) was 10.7 for serious adverse events , 3.3 for serious infections , 7.4 for herpes zoster ( serious and non-serious ) and 1.2 for malignancies ( excluding non-melanoma skin cancer ) . Mean changes from baseline ( start of the index study ) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib . ACR20/50/70 response rates , DAS-defined remission rates and HAQ-DI scores were sustained through to study completion . Conclusions Tofacitinib ( with or without background methotrexate ) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis . The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population .Trial registration Clinical trials.gov NCT00661661 . Registered 7 February 2008 BACKGROUND & AIMS The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis ( UC ) have not been evaluated previously . METHODS This r and omized , double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy , azathioprine monotherapy , or the 2 drugs combined in  tumor necrosis factor-a antagonist-naive adults with moderate to severe UC . Patients were assigned r and omly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0 , 2 , 6 , and 14 plus daily oral placebo capsules ; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule ; or combination therapy with the 2 drugs .  Corticosteroid-free clinical remission ( primary end point , week 16 ) was evaluated at weeks 8 and 16 . The study was terminated before the enrollment target was reached . RESULTS A total of 239 patients were included in efficacy analyses . Baseline characteristics were similar between treatment groups . Corticosteroid-free remission at week 16 was achieved by 39.7 % ( 31 of 78 ) of patients receiving infliximab/azathioprine , compared with 22.1 % ( 17 of 77 ) receiving infliximab alone(P = .017 ) and 23.7 % ( 18 of 76 ) receiving azathioprine alone(P = .032 ) . Mucosal healing at week 16 occurred in 62.8 % ( 49 of 78 ) of patients receiving infliximab/azathioprine , compared with 54.6 % ( 42 of 77 ) receiving infliximab ( P = .295 ) and 36.8 % ( 28 of 76 ) receiving azathioprine ( P = .001 ) . Serious infections occurred in 2 patients ( 1 patient receiving infliximab , and 1 patient receiving azathioprine ) . CONCLUSIONS Anti – tumor necrosis factor-a – naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy . Combination therapy led to significantly better mucosal healing than azathioprine monotherapy . Clinical Trials.gov number , NCT00537316 Background : Infliximab ( IFX ) , adalimumab ( ADA ) , and certolizumab pegol ( CZP ) have similar efficacy in induction and maintenance of clinical remission in Crohn 's disease ( CD ) . Given the comparable nature of these drugs , patient preferences may influence the choice of the product . We aim ed to identify factors that may contribute to CD patients ' decision in selecting one anti‐tumor necrosis factor ( TNF ) agent over the others . Methods : A prospect i ve survey was performed among anti‐TNF‐naïve CD patients . Prior to completion of a question naire , patients were provided with a written description of the three anti‐TNF agents , focusing on indications , mode of administration , side effects , and scientific evidence of efficacy and safety for each drug . Results : One hundred patients ( 47 females , mean age 45 ± 16 years , range 19–81 ) with an ileal , colonic , or ileocolonic ( 33 % , 40 % , and 27 % , respectively ) disease location completed the question naire . Based on the information provided , 36 % of patients preferred ADA , 28 % CZP , and 25 % IFX , whereas 11 % were undecided . The patients ' decision in selecting a specific anti‐TNF drug was influenced by the following factors : ease of use ( 69 % ) , time required for therapy ( 34 % ) , time interval between application of the drug ( 31 % ) , scientific evidence for efficacy ( 19 % ) , and fear of syringes ( 10 % ) . Conclusions : The majority of patients preferred anti‐TNF medications that were administered by subcutaneous injection rather than by intravenous infusion . Ease of use and time required for therapy were two major factors influencing the patients ' selection of a specific anti‐TNF drug . Patients ' individual preferences should be taken into account when prescribing anti‐TNF drugs . ( Inflamm Bowel Dis 2012 BACKGROUND & AIMS : The efficacy and safety of vedolizumab , a humanized immunoglobulin G1 monoclonal antibody against the integrin & agr;4&bgr;7 , were demonstrated in multicenter , phase 3 , r and omized , placebo‐controlled trials in patients with moderately to severely active ulcerative colitis ( UC ) or Crohn 's disease . We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC , based on past exposure to anti – tumor necrosis factor‐&agr ; ( TNF ) antagonists . METHODS : We performed a post hoc analysis of data from the GEMINI 1 study , collected from 464 patients who received vedolizumab or placebo but had not received a previous TNF antagonist ( naive to TNF antagonists ) and 367 patients with an inadequate response , loss of response , or intolerance to TNF antagonists ( failure of TNF antagonists ) . Predefined outcomes of GEMINI 1 were evaluated in these sub population s. RESULTS : At Week 6 , there were greater absolute differences in efficacy  between vedolizumab and placebo in patients naive to TNF antagonists than 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective . One additional treatment may be tofacitinib ( CP-690,550 ) , an oral inhibitor of Janus kinases 1 , 2 , and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 , which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2 , 4 , 7 , 9 , 15 , and 21 . These cytokines are integral to lymphocyte activation , function , and proliferation . METHODS In a double-blind , placebo-controlled , phase 2 trial , we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis . Patients were r and omly assigned to receive tofacitinib at a dose of 0.5 mg , 3 mg , 10 mg , or 15 mg or placebo twice daily for 8 weeks . The primary outcome was a clinical response at 8 weeks , defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity ( possible score , 0 to 12 , with higher scores indicating more severe disease ) of 3 or more and a relative decrease from baseline of 30 % or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 . RESULTS The primary outcome , clinical response at 8 weeks , occurred in 32 % , 48 % , 61 % , and 78 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.39 ) , 3 mg ( P=0.55 ) , 10 mg ( P=0.10 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 42 % of patients receiving placebo . Clinical remission ( defined as a Mayo score ≤2 , with no subscore > 1 ) at 8 weeks occurred in 13 % , 33 % , 48 % , and 41 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.76 ) , 3 mg ( P=0.01 ) , 10 mg ( P<0.001 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 10 % of patients receiving placebo . There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol . Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 . CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00787202 . ) 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 Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis . Here , tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented . Methods Study A3921041 was a multi-centre , open-label , long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate .  Patients received tofacitinib 5 mg twice daily ( BID ) or tofacitinib 10 mg BID . Dose adjustment of tofacitinib during treatment period , and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted . Primary endpoints were adverse events , laboratory parameters and vital signs . Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates , Disease Activity Score (DAS)28 - 4(erythrocyte sedimentation rate (ESR))<2.6 response rate ( DAS-defined remission ) and Health Assessment Question naire-Disability Index ( HAQ-DI ) score . Safety and efficacy data were assessed throughout the study . Results A total of 486 patients were recruited and treated ( 1439.9 patient-years of exposure ) . 308 patients completed the study .  Median ( range ) duration of treatment in this extension study was 1185 ( 5–2016 ) days . 476 patients ( 97.9 % ) experienced adverse events ; the majority of which ( 97.8 % ) were of mild or moderate severity . The two most common treatment-emergent adverse events were nasopharyngitis ( n = 293 , 60.3 % ) and herpes zoster ( n = 94 , 19.3 % ) . For all tofacitinib-treated patients , the incidence rate ( patients with events per 100 patient-years ) was 10.7 for serious adverse events , 3.3 for serious infections , 7.4 for herpes zoster ( serious and non-serious ) and 1.2 for malignancies ( excluding non-melanoma skin cancer ) . Mean changes from baseline ( start of the index study ) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib . ACR20/50/70 response rates , DAS-defined remission rates and HAQ-DI scores were sustained through to study completion . Conclusions Tofacitinib ( with or without background methotrexate ) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis . The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population .Trial registration Clinical trials.gov NCT00661661 . Registered 7 February 2008 BACKGROUND & AIMS The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis ( UC ) have not been evaluated previously . METHODS This r and omized , double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy , azathioprine monotherapy , or the 2 drugs combined in  tumor necrosis factor-a antagonist-naive adults with moderate to severe UC . Patients were assigned r and omly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0 , 2 , 6 , and 14 plus daily oral placebo capsules ; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule ; or combination therapy with the 2 drugs .  Corticosteroid-free clinical remission ( primary end point , week 16 ) was evaluated at weeks 8 and 16 . The study was terminated before the enrollment target was reached . RESULTS A total of 239 patients were included in efficacy analyses . Baseline characteristics were similar between treatment groups . Corticosteroid-free remission at week 16 was achieved by 39.7 % ( 31 of 78 ) of patients receiving infliximab/azathioprine , compared with 22.1 % ( 17 of 77 ) receiving infliximab alone(P = .017 ) and 23.7 % ( 18 of 76 ) receiving azathioprine alone(P = .032 ) . Mucosal healing at week 16 occurred in 62.8 % ( 49 of 78 ) of patients receiving infliximab/azathioprine , compared with 54.6 % ( 42 of 77 ) receiving infliximab ( P = .295 ) and 36.8 % ( 28 of 76 ) receiving azathioprine ( P = .001 ) . Serious infections occurred in 2 patients ( 1 patient receiving infliximab , and 1 patient receiving azathioprine ) . CONCLUSIONS Anti – tumor necrosis factor-a – naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy . Combination therapy led to significantly better mucosal healing than azathioprine monotherapy . Clinical Trials.gov number , NCT00537316 Background : Infliximab ( IFX ) , adalimumab ( ADA ) , and certolizumab pegol ( CZP ) have similar efficacy in induction and maintenance of clinical remission in Crohn 's disease ( CD ) . Given the comparable nature of these drugs , patient preferences may influence the choice of the product . We aim ed to identify factors that may contribute to CD patients ' decision in selecting one anti‐tumor necrosis factor ( TNF ) agent over the others . Methods : A prospect i ve survey was performed among anti‐TNF‐naïve CD patients . Prior to completion of a question naire , patients were provided with a written description of the three anti‐TNF agents , focusing on indications , mode of administration , side effects , and scientific evidence of efficacy and safety for each drug . Results : One hundred patients ( 47 females , mean age 45 ± 16 years , range 19–81 ) with an ileal , colonic , or ileocolonic ( 33 % , 40 % , and 27 % , respectively ) disease location completed the question naire . Based on the information provided , 36 % of patients preferred ADA , 28 % CZP , and 25 % IFX , whereas 11 % were undecided . The patients ' decision in selecting a specific anti‐TNF drug was influenced by the following factors : ease of use ( 69 % ) , time required for therapy ( 34 % ) , time interval between application of the drug ( 31 % ) , scientific evidence for efficacy ( 19 % ) , and fear of syringes ( 10 % ) . Conclusions : The majority of patients preferred anti‐TNF medications that were administered by subcutaneous injection rather than by intravenous infusion . Ease of use and time required for therapy were two major factors influencing the patients ' selection of a specific anti‐TNF drug . Patients ' individual preferences should be taken into account when prescribing anti‐TNF drugs . ( Inflamm Bowel Dis 2012 BACKGROUND & AIMS : The efficacy and safety of vedolizumab , a humanized immunoglobulin G1 monoclonal antibody against the integrin & agr;4&bgr;7 , were demonstrated in multicenter , phase 3 , r and omized , placebo‐controlled trials in patients with moderately to severely active ulcerative colitis ( UC ) or Crohn 's disease . We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC , based on past exposure to anti – tumor necrosis factor‐&agr ; ( TNF ) antagonists . METHODS : We performed a post hoc analysis of data from the GEMINI 1 study , collected from 464 patients who received vedolizumab or placebo but had not received a previous TNF antagonist ( naive to TNF antagonists ) and 367 patients with an inadequate response , loss of response , or intolerance to TNF antagonists ( failure of TNF antagonists ) . Predefined outcomes of GEMINI 1 were evaluated in these sub population s. RESULTS : At Week 6 , there were greater absolute differences in efficacy  between vedolizumab and placebo in patients naive to TNF antagonists than 
    Output:
    