***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 assess efficacy , safety , and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis ( MS ) ( clinical ly isolated syndrome ) . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled trial . Patients with a first clinical demyelinating event and at least two clinical ly silent brain MRI lesions were r and omized to interferon beta-1b ( IFNB-1b ) 250 mug subcutaneously ( SC ) every other day ( EOD ) ( n = 292 ) or placebo ( n = 176 ) , until clinical ly definite MS ( CDMS ) was diagnosed or they had been followed for 24 months . RESULTS After 2 years , 45 % of placebo patients had converted to CDMS ( Kaplan-Meier estimate ; primary outcome measure ) and 85 % fulfilled the McDonald criteria ( co- primary outcome measure ) . Overall interferon beta-1b delayed the time to diagnosis of CDMS ( p < 0.0001 ) and McDonald MS ( p < 0.00001 ) . Hazard ratios ( 95 % CI ) were 0.50 ( 0.36 to 0.70 ) for CDMS and 0.54 ( 0.43 to 0.67 ) for McDonald MS favoring treatment with IFNB-1b . Treatment was well tolerated , as indicated by the low rate of patients dropping out of the study before CDMS was reached ( 6.6 % overall , 7.2 % in the IFNB-1b group ) . CONCLUSIONS Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinical ly definite multiple sclerosis , and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis Safety , tolerability and efficacy profiles of interferon beta ( IFNβ ) therapy in relapsing multiple sclerosis ( MS ) has been widely verified both in trial setting s and in daily clinical practice . However , for a variable percentage of treated patients , it remains only partially effective . In this study , we reported the post-marketing experience of the efficacy of IFNβ therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of “ La Sapienza University ” in Rome . In this cohort we also sought clinical and para clinical variables responsible for the clinical course of MS during IFNβ therapy .  Patients that received treatment with one of the IFNβ formulations for at least 1 year were included  . Clinical outcomes ( i. e. , relapses and disability score ) were monitored throughout the entire study period . Magnetic resonance imaging ( MRI ) scans were performed twice for each subject : at baseline and after 1 year of therapy . The occurrence of more than one relapse during the study period or a sustained disability progression in the Exp and ed Disability Status Scale ( EDSS ) score were considered as criteria for the definition of suboptimal clinical response to IFNβ therapy . During IFNβ therapy ( number of patients 242 , mean length of treatment 4.3±2.3 years ) a reduction in the annualised relapse rate of 59 % ( p<0.001 ) was observed . Eighty-six patients ( 35 % ) fulfilled the criterion for defining “ suboptimal responder ” on the basis of relapses , and 69 ( 28.5 % ) did the same on the basis of EDSS sustained progression . Twenty-seven ( 11.1 % ) patients showed both an EDSS progression and two or more relapses . The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period ( OR for enhancing lesions and relapses 3.6 ; OR for new T2 lesion and relapses 2.8 ) . The present post-marketing experience confirms the efficacy of IFNβ in modifying the natural course of MS and encourages the use of para clinical variables measuring sub clinical disease activity as surrogate markers to monitor the clinical course of MS during IFNβ therapy Background Interferon-beta ( IFNβ ) is used to inhibit disease activity in multiple sclerosis ( MS ) , but its mechanisms of action are incompletely understood , individual treatment response varies , and biological markers predicting response to treatment have yet to be identified . Methods The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good ( n = 70 ) or poor response ( n = 15 ) . Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes ( IRGs ) . Results The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes . The molecular response was strikingly stable for individuals for as long as 24 months , however , suggesting an individual ‘ IFN response fingerprint ’ . Unexpectedly , patients with poor response showed an exaggerated molecular response . IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections . Conclusion MS patients exhibit individually unique but temporally stable biological responses to IFNβ . Poor treatment response is not explained by the duration of biological effects or the specific genes induced . Rather , individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections . We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity . The findings suggest a strategy for biologically based , rational use of IFNβ for individual MS patients Abstract Whereas the effect of interferons ( IFNs ) on magnetic resonance imaging ( MRI ) outcome measures in patients with multiple sclerosis ( MS ) has been convincingly shown , little work has been done to define the between – patient heterogeneity of treatment response . Our aim was to assess the distribution of the effect of IFNβ– 1b in terms of reduction of active T2 lesions in patients with MS . Using a fixed and a r and om effects model , we investigated the distribution of active T2 lesions reduction over a three – year follow up in response to treatment with 250mcg IFNβ–1b every other day in 695 patients with a complete MRI data –set of the 718 ( 97 % ) enrolled in the European , multicenter , r and omised , double – blind , placebocontrolled trial of secondary progressive MS.The two statistical models consistently showed that the betweenpatient response to IFNβ–1b , in terms of reduction of active T2 lesions , is highly heterogeneous . Whereas treated patients have a high probability ( more than 65 % ) of showing an active T2 lesion reduction equal to or greater than 60 % , there is also a 7 % probability for treated patients not to show any reduction of MRI – detected disease activity during the course of the trial or even to have an increase of T2 active lesions . This study might be regarded as a first step toward the definition of markers potentially useful to identify IFNβ treatment responders and non – responders with regard to T2 lesion activity Objective : To prospect ively vali date MRI activity and neutralising anti-interferon antibody ( NAb ) during the first 6 months of interferon β treatment as response indicators in multiple sclerosis ( MS ) . Methods : Patients with relapsing – remitting MS were followed during the first 2 years of treatment . Neurological assessment s were performed every 3 months or when a relapse was suspected . MRI scans performed at baseline and at 3 , 4 , 5 and 6 months after the start of treatment were assessed central ly for disease activity : new T2 or gadolinium enhancing T1 lesions . NAb were assessed using the MxA protein assay ; positivity was defined as two consecutive titres ⩾20 NU/ml . We evaluated the predictivity of an active scan , NAb positivity , or both , during the first 6 months of treatment , on the occurrence of clinical disease activity in the following 18 months . Results : 147 patients were assessed at 16 centres . Predictivity parameters ( with confidence intervals ) were as follows : active scan , sensitivity ( SN ) 52 % ( 34–69 % ) , specificity ( SP ) 80 % ( 65–91 % ) , negative predictive value ( NPV ) 73 % ( 58–77 % ) , positive predictive value ( PPV ) 62 % ( 42–79 % ) , p = 0.002 ; NAb positivity , SN 71 % ( 45–88 % ) , SP 66 % ( 55–76 % ) , NPV 92 % ( 82–97 % ) , PPV 29 % ( 16–45 % ) , p = 0.01 ; active scan and NAb positivity , SN 71 % ( 38–91 % ) , SP 86 % ( 73–94 % ) , NPV 94 % ( 86–98 % ) , PPV 50 % ( 29–70 % ) , p = 0.0003 . Conclusions : MRI activity and NAb occurrence during the first 6 months of interferon β treatment were reliable predictors of long term clinical response , particularly when combined . Patients with negative predictors showed a less than 10 % risk of developing clinical activity . Patients with positive predictors showed a 50 % risk of further clinical activity . These patients need to be followed carefully with further MRI and NAb tests BACKGROUND Interferon beta reduces activity in multiple sclerosis as measured clinical ly and by magnetic resonance imaging ( MRI ) . We assessed the effect of interferon beta-1a on the occurrence of relapses in patients after first presentation with neurological events , who are at high risk of conversion to clinical ly definite multiple sclerosis . METHODS Eligible patients had had a first episode of neurological dysfunction suggesting multiple sclerosis within the previous 3 months and had strongly suggestive brain MRI findings . Patients were r and omly assigned interferon beta-1a  22 microg or placebo  subcutaneously once weekly for 2 years . Neurological and clinical assessment s were done every 6 months and brain MRI every 12 months . Analyses excluded one patient assigned placebo who received no study injections . FINDINGS 241 ( 78 % ) of 308 r and omised patients received study treatment for 2 years ; 278 ( 90 % ) remained in the study until termination . 57 ( 85 % ) of 67 who stopped therapy did so after conversion to clinical ly definite multiple sclerosis . Fewer patients developed clinical ly definite multiple sclerosis in the interferon group than in the placebo group ( 52/154 [ 34 % ] vs 69/154 [ 45 % ] ; p=0.047 ) . The time at which 30 % of patients had converted to clinical ly definite multiple sclerosis was 569 days in the interferon group and 252 in the placebo group ( p=0.034 ) . The annual relapse rates were 0.33 and 0.43 ( p=0.045 ) . The number of new T2-weighted MRI lesions and the increase in lesion burden were significantly lower with active treatment . INTERPRETATION Interferon beta-1a treatment at an early stage of multiple sclerosis had significant positive effects on clinical and MRI outcomes IFN-beta is effective in reducing relapses and magnetic resonance imaging ( MRI ) lesions in multiple sclerosis ( MS ) . It is assumed that individual therapeutic responses vary , but methods to identify IFN-beta responsiveness have not been vali date d. Our objective was to evaluate methods to classify IFN-beta responder status using relapses and MRI lesions . Data was analyzed from 172 patients who were followed up in a placebo-controlled clinical trial of IFN-beta1a for 2 years . Patients were classified as responders or nonresponders using ( 1 ) the number of relapses during the 2-year trial ; ( 2 ) the number of new T2 lesions after 2 years ; and ( 3 ) the number of gadolinium-enhancing lesions at year 1 and year 2 on study . Outcomes included 2-year change in the Exp and ed Disability Status Scale , Multiple Sclerosis Functional Composite , and brain parenchymal fraction . We found that subgroups with high on- study relapse numbers had more disease progression , differences between responder subgroups were similar in the IFN-beta1a and placebo arms . In contrast , subgroups with high numbers of new MRI lesions had significantly more disease progression only in the IFN-beta1a arm . Baseline characteristics failed to account for differential outcome . New MRI lesion activity during IFN-beta1a treatment correlates with poor response to IFN-beta1a . MRI classification may facilitate rational therapeutic decisions , better clinical trial design s , and studies correlating biomarkers with therapeutic response Background and objective Several criteria for treatment response to interferon beta ( IFNβ ) have been proposed , although there is no consensus among different investigators . Hence , the aim of this study was to investigate magnetic resonance imaging ( MRI ) and clinical predictors of response during the first 12 months of therapy . Methods This is a prospect i ve and longitudinal study of relapsing-remitting multiple sclerosis ( RRMS ) patients treated with IFNβ .  Patients were classified based on the presence of new lesions on MRI , relapses , confirmed disability increase , or combinations of all these variables after 1 year of therapy . Regression analysis was performed in order to identify variables of response after a follow-up of 3 years . Results We included 222 RRMS patients . The logistic model demonstrated that only the combination of new active lesions on MRI with the presence of relapses ( OR 4.4 ; 9 
    Output:
    
Results : Patients with MRI evidence of poor response to IFN-&bgr ; treatment as defined by either ≥2 new hyperintense T2 lesions or new gadolinium-enhancing lesions had significantly increased risk of both future relapses and progression as defined by the Exp and ed Disability Status Scale .
Previous evidence has shown this not to be the case in placebo arms of clinical trials .
Conclusions : For those patients starting IFN-&bgr ;  , early MRI , within 6 to 24 months after starting treatment , has the potential to provide important information when counseling patients about the likelihood of future treatment failure .