***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: Objective To investigate the relationship between serum etanercept levels and clinical response . Methods In 292 etanercept-treated patients with rheumatoid arthritis clinical and pharmacological data were determined at baseline and after 1 , 4 and 6 months of etanercept treatment . Differences in  etanercept levels between good , moderate and European League Against Rheumatism ( EULAR ) non-responders were assessed after 6 months of therapy . Results After 6 months of therapy etanercept levels were significantly higher in good responders ( median ( IQR ) 3.78 ( 2.53–5.17 ) ) compared with both moderate 3.10 ( 2.12–4.47 ) and EULAR non-responders 2.80 ( 1.27–3.93 ) ( all p<0.05 ) . There was a significant association between clinical response and serum etanercept levels ( regression coefficient 0.54 , 95 % CI 0.21 to 0.86 , p=0.001 ) . When patients were categorised into quartiles according to the height of etanercept levels , the lowest quartile ( etanercept level < 2.1 mg/l ) comprised 40 % of all non-responders . The highest quartile ( etanercept level > 4.7 mg/l ) comprised 35 % of all good EULAR responders . Anti-etanercept antibodies were detected in none of the sera . Conclusion The authors demonstrated that lower etanercept levels were associated with non-response . Therapeutic drug monitoring and the possibility of the adjusted dosing regimes in the selected groups of patients should be investigated further as a possible tool to optimise treatment with etanercept BACKGROUND & AIMS Infliximab , a tumor necrosis factor antagonist , is effective for treating patients with Crohn 's disease ( CD ) and ulcerative colitis ( UC ) . We aim ed to determine whether dosing based on therapeutic drug monitoring increases rate of remission and whether continued concentration-based dosing is superior to clinical ly based dosing of infliximab for maintaining remission in patients with CD and UC . METHODS We performed a 1-year r and omized controlled trial at a tertiary referral center , including 263 adults ( 178 with CD and 85 with UC ) with stable responses to maintenance infliximab therapy . Doses were escalated or reduced using an algorithm to reach a target trough concentration ( TC ) of 3 - 7 μg/mL in all patients ( optimization phase ) . Patients were r and omly assigned ( 1:1 ) to groups that received infliximab dosing based on their clinical features ( n = 123 ) or continued dosing based on TCs ( n = 128 ) ( maintenance phase ) . The primary end point was clinical and biochemical remission at 1 year after the optimization phase . RESULTS At screening , 115 of 263 patients had a TC of infliximab of 3 - 7 μg/mL ( 43.7 % ) . Of 76 patients with TCs <3 μg/mL , 69 patients ( 91 % ) achieved TCs of 3 - 7 μg/mL after dose escalation . This result ed in a higher proportion of CD patients in remission than before dose escalation ( 88 % vs 65 % ; P = .020 ) and a decrease in the median concentration of C-reactive protein , compared with before the dose increase ( 3.2 vs 4.3 mg/L ; P < .001 ) ; these changes were not observed in patients with UC . Of 72 patients with TCs > 7 μg/mL , 67 patients ( 93 % ) achieved TCs of 3 - 7 μg/mL after dose reduction . This result ed in a 28 % reduction in drug cost from before dose reduction ( P < .001 ) . Sixty-six percent of patients whose dosing was based on clinical features and 69 % whose dosing was based on TC achieved remission , the primary end point ( P = .686 ) . Disease relapsed in 21 patients who received clinical ly based dosing ( 17 % ) and 9 patients who received concentration-based dosing ( 7 % ) ( P = .018 ) . CONCLUSIONS Targeting patients ' infliximab TCs to 3 - 7 μg/mL results in a more efficient use of the drug . After dose optimization , continued concentration-based dosing was not superior to clinical ly based dosing for achieving remission after 1 year , but was associated with fewer flares during the course of treatment . Clinical TrialsRegister.eu number : 2011 - 002061 - 38 BACKGROUND We did a r and omised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn 's disease who respond to a single infusion of infliximab .  METHODS 573 patients with a score of at least 220 on the Crohn 's disease activity index ( CDAI ) received a 5 mg/kg intravenous infusion of infliximab at week 0 . After assessment of response at week 2 , patients were r and omly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 ( group I ) , repeat infusions of 5 mg/kg infliximab at the same timepoints ( group II ) , or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg ( group III ) . The prespecified co- primary endpoints were the proportion of patients who responded at week 2 and were in remission ( CDAI < 150 ) at week 30 and the time to loss of response up to week 54 in patients who responded . Analyses of the co- primary endpoints were by intention to treat . FINDINGS 335 ( 58 % ) patients responded to a single infusion of infliximab within 2 weeks . At week 30 , 23 of 110 ( 21 % ) group I patients were in remission , compared with 44 of 113 ( 39 % ) group II ( p=0.003 ) and 50 of 112 ( 45 % ) group III ( p=0.0002 ) patients . Thus , patients in groups II and III combined were more likely to sustain clinical remission than patients in group I ( odds ratio 2.7 , 95 % CI 1.6 - 4.6 ) . Throughout the 54-week trial , the median time to loss of response was 38 weeks ( IQR 15 to > 54 ) and more than 54 weeks ( 21 to > 54 ) for groups II and III , respectively , compared with 19 weeks ( 10 - 45 ) for group I ( p=0.002 and p=0.0002 , respectively ) .  Infliximab safety was consistent with that seen in other trials of infliximab in Crohn 's disease and rheumatoid arthritis . In particular , the incidence of serious infections was similar across treatment groups . INTERPRETATION Patients with Crohn 's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54 , to discontinue corticosteroids , and to maintain their response for a longer period of time , if infliximab treatment is maintained every 8 weeks BACKGROUND TNF inhibitors have improved treatment of Crohn 's disease , ulcerative colitis , spondyloarthritis , rheumatoid arthritis , psoriatic arthritis , and chronic plaque psoriasis , but are expensive therapies . The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy , safety , and immunogenicity . METHODS The study is a r and omised , non-inferiority , double-blind , phase 4 trial with 52 weeks of follow-up . Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation . Patients with informed consent were r and omised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment , with unchanged dosing regimen . Data were collected at infusion visits in 40 Norwegian study centres . Patients , assessors , and patient care providers were masked to treatment allocation . The primary endpoint was disease worsening during 52-week follow-up .  394 patients in the primary per- protocol set were needed to show a non-inferiority margin of 15 % , assuming 30 % disease worsening in each group . This trial is registered with Clinical Trials.gov , number NCT02148640 . FINDINGS Between Oct 24 , 2014 , and July 8 , 2015 , 482 patients were enrolled and r and omised ( 241 to infliximab originator , 241 to CT-P13 group ; one patient was excluded from the full analysis and safety set for CT-P13 ) and 408 were included in the per- protocol set ( 202 in the infliximab originator group and 206 in the CT-P13 group ) . 155 ( 32 % ) patients in the full analysis set had Crohn 's disease , 93 ( 19 % ) had ulcerative colitis , 91 ( 19 % ) had spondyloarthritis , 77 ( 16 % ) had rheumatoid arthritis , 30 ( 6 % ) had psoriatic arthritis , and 35 ( 7 % ) had chronic plaque psoriasis . Disease worsening occurred in 53 ( 26 % ) patients in the infliximab originator group and 61 ( 30 % ) patients in the CT-P13 group ( per- protocol set ; adjusted treatment difference -4·4 % , 95 % CI -12·7 to 3·9 ) . The frequency of adverse events was similar between groups ( for serious adverse events , 24 [ 10 % ] for infliximab originator vs 21 [ 9 % ] for CT-P13 ; for overall adverse events , 168 [ 70 % ] vs 164 [ 68 % ] ; and for adverse events leading to discontinuation , nine [ 4 % ] vs eight [ 3 % ] , respectively ) . INTERPRETATION The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15 % . The study was not powered to show non-inferiority in individual diseases . FUNDING Norwegian Ministry of Health and Care Services BACKGROUND AND AIMS The biosimilar of Remicade ® , CT-P13 , recently entered the European market . Clinical data on switching from Remicade ® to CT-P13 in inflammatory bowel disease [ IBD ] are scarce . We aim ed to prospect ively investigate efficacy , safety , pharmacokinetic profile , and immunogenicity following a switch from Remicade ® to CT-P13 in IBD patients . METHODS  Remicade ® -treated IBD patients at the Radboud university medical centre who switched to CT-P13 were included in this prospect i ve observational cohort study . Primary endpoint was change in Harvey-Bradshaw Index for Crohn 's disease [ CD ] and Simple Clinical Colitis Activity Index for ulcerative colitis [ UC ] at week 16 . We measured C-reactive protein [ CRP ] , faecal calprotectin [ FCP ] , infliximab trough level [ TL ] and anti-drug antibodies [ ADAs ] and documented adverse events . RESULTS Our cohort consisted of 83 patients ( 28 males , 57 CD , 24 UC , 2 IBD-unclassified [ IBD-U ] ) . The median age was 36 years , range 18 - 79 . Median change in disease activity was 0 [ range -23 to + 7 ] for CD and 0 [ range -3 to + 6 ] for UC/IBD-U. Median CRP and FCP levels did not change significantly during follow-up . Median TL increased from 3.5 µg/ml [ range 0 - 18 ] to 4.2 µg/ml [ range 0 - 21 ] at week 16 [ p = 0.010 ] . Two patients developed a new detectable ADA response during follow-up and five patients discontinued CT-P13 . No serious adverse events occurred . CONCLUSIONS We demonstrated that switching from Remicade ® to CT-P13 in a real-life cohort of IBD patients did not have a significant impact on short-term clinical outcomes . These results suggest that switching from Remicade ® to CT-P13 for the treatment of IBD is feasible OBJECTIVE To evaluate the efficacy , pharmacokinetics , immunogenicity , and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody ( cA2 ) ( infliximab ; Remicade , Centocor , Malvern , PA ) given alone or in combination with low-dose methotrexate ( MTX ) in rheumatoid arthritis ( RA ) patients . METHODS In a 26-week , double-blind , placebo-controlled , multicenter trial , 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were r and omized to 1 of 7 groups of 14 - 15 patients each . The patients received either intravenous cA2 at  
    Output:
    
Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease .
Although prospect i ve controlled trials yield little conclusive evidence of its benefits , there is growing acceptance of its value in clinical practice