***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: Abstract Background : Several predictors for treatment failure to interferon-beta ( IFN-beta ) have been proposed ; however , brain atrophy has not been well studied . Methods : In this prospect i ve and longitudinal study , all consecutive relapsing – remitting multiple sclerosis ( RRMS ) patients treated with sc IFN-beta-1a  were included . Confirmed disability progression or a new relapse between weeks 48 and 144 after beginning with IFN-beta was considered as treatment non-response . EDSS progression , relapses , number of active lesions at 1 year ( new or enlarging T2-weighted plus gadolinium-enhancing lesions , categorized in > 2 or ≤ 2 ) , and brain parenchymal fraction ( % BVC ) volume change within the initial year of treatment were used as predictive factors . Cox regression model was adjusted for age , gender , and disease duration . Results : Seventy-one patients were included ( 71·8 % female ) with a follow-up of 144 weeks . Thirty-four ( 48 % ) fulfilled criteria of non-response to IFN-beta treatment . The model showed : ( 1 ) relapses+disability progression : HR = 4·6 , 95 % IC : 3·1–6·7 ( P < 0·001 ) ; ( 2 ) relapses+BVC decrease : HR = 4·1 , 95 % IC : 3·2–7·3 ( P = 0·001 ) ; ( 3 ) relapses+disability progression+new active lesions : HR = 10·1 , 95 % IC : 7·1–15·2 ( P < 0·001 ) ; and ( 4 ) relapses+disability progression+new active lesions+BVC decrease : HR = 14·4 , 95 % IC : 11·4–21·2 ( P < 0·001 ) . Conclusions : Adding BVC measures to previously described predictive failure factors may increase sensitivity to early identify non-responder patients to IFN-beta-1a in the second and third years of therapy Background : We employed clinical and magnetic resonance imaging ( MRI ) measures in combination , to assess patient responses to interferon in multiple sclerosis . Objective : To optimize and vali date a scoring system able to discriminate responses to interferon treatment in patients with relapsing – remitting multiple sclerosis ( RRMS ) . Methods : Our analysis included two large , independent data sets of RRMS patients who were treated with interferons that included 4-year follow-up data . The first data set ( “ training set ” ) comprised of 373 RRMS patients from a r and omized clinical trial of subcutaneous interferon beta-1a .  The second ( “ validation set ” ) included an observational cohort of 222 RRMS patients treated with different interferons .  The new scoring system , a modified version of that previously proposed by Rio et al. , was first tested on the training set , then vali date d using the validation set . The association between disability progression and risk group , as defined by the score , was evaluated by Kaplan Meier survival curves and Cox regression , and quantified by hazard ratios ( HRs ) . Results : The score ( 0–3 ) was based on the number of new T2 lesions ( > 5 ) and clinical relapses ( 0,1 or 2 ) during the first year of therapy . The risk of disability progression increased with higher scores . In the validation set , patients with score of 0 showed a 3-year progression probability of 24 % , while those with a score of 1 increased to 33 % ( HR = 1.56 ; p = 0.13 ) , and those with score greater than or equal to 2 increased to 65 % ( HR = 4.60 ; p < 0.001 ) . Conclusions : We report development of a simple , quantitative and complementary tool for predicting responses in  interferon-treated patients that could help clinicians make treatment decisions The accepted st and ard treatment of relapsing multiple sclerosis consists of medications for disease symptoms , including treatment for acute exacerbations . However , currently there is no therapy that alters the progression of physical disability associated with this disease . The purpose of this study was to determine whether interferon beta‐1a could slow the progressive , irreversible , neurological disability of relapsing multiple sclerosis . Three hundred one patients with relapsing multiple sclerosis were r and omized into a double‐blinded , placebo‐controlled , multicenter phase I11 trial of interferon beta‐la . Interferon beta‐la , 6.0 million units ( 30 μg ) , was administered by intramuscular injection weekly . The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Exp and ed Disability Status Scale ( EDSS )  . Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression ( p equals ; 0.02 ) . The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9 % in the placebo group and 21.9 % in the interferon beta‐la‐treated group . Patients treated with interferon beta‐la also had significantly fewer exacerbations ( p = 0.03 ) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images ( pvalues ranging between 0.02 and 0.05 ) . Over 2 years , the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients . There were no major adverse events related to treatment . Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients  by reducing the accumulation of permanent physical disability , exacerbation frequency , and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images . This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis OBJECTIVES Criteria for Treatment Optimization Recommendations ( TOR ) for patients with multiple sclerosis ( MS ) identify suboptimal response to disease-modifying treatment ( DMT ) . The Canadian TOR ( CanTOR ) were used to indicate recommendations for treatment switches or treatment maintenance based on relapse , disease progression and magnetic resonance imaging ( MRI ) criteria in patients . We assessed concordance between the TOR and clinicians ' decisions regarding treatment response and identified prevalence of patients with MS receiving DMT meeting medium/high levels of concern according to TOR . METHODS Prospect i ve baseline and end-of- study assessment s of patients with relapsing-remitting MS ( RRMS ) or clinical ly isolated syndrome were conducted in this open-label , 12-month , Phase IV , observational Canadian study . RESULTS Data were reported for 184 patients ( female 72 % , mean age 39 years ) of which 96 % had RRMS . The TOR criteria identified 19 ( 10.3 % ) patients with suboptimal response to treatment . Twelve patients had ≥1 high level of concern . Two patients had ≥2 medium levels of concern . Concordance between TOR and clinician decision in maintaining treatment was 95.3 % . Where treatment change was recommended by the TOR , concordance was 29.4 % . Clinicians identified the  TOR as the principal reason for changing treatment in 50.0 % of cases where the TOR identified suboptimal response . The TOR were considered useful by 70.6 % of clinicians when treatment optimization was recommended and by 55.3 % when maintaining treatment was recommended . CONCLUSIONS The TOR criteria can identify suboptimal response in this patient cohort . Concordance between TOR and clinician decision was high when maintaining treatment was recommended . Usefulness of the TOR was most apparent when treatment optimization was recommended Proposed beta-interferon ( IFNβ ) treatment failure criteria for patients with relapsing-remitting multiple sclerosis ( RRMS ) have not been vali date d in clinical practice . This study aim ed to establish ( a ) whether IFNβ attenuated accumulation of fixed disability in comparison to a cohort of matched historical control subjects from the Sylvia Lawry centre for MS research , and ( b ) whether relapse-based treatment failure criteria or clinical and demographic variables had predictive value for the accumulation of fixed disability . Of the 175 IFNβ-treated RRMS patients , 60 ( 34 % ) developed accumulation of fixed disability over a median of five years follow-up , which was significantly less than the rate of accumulation of fixed disability in the control group ( P<0.0001 ) . Any relapse in the treatment period predicted accumulation of fixed disability with a sensitivity of 80 % and specificity of 43 % ; patients totally relapse free were less likely to develop accumulation of fixed disability ( P < 0.002 ) . Multivariate analysis confirmed that a greater risk of accumulation of fixed disability was conferred by a higher Exp and ed Disability Status Scale ( EDSS ) score starting IFNβ ( P=0.02 ) , and by failure of IFNβ to completely suppress relapses ( P=0.004 ) . In conclusion , IFNβ therapy reduced the accumulation of fixed disability in a cohort of RRMS patients , followed for a median of five years . Higher baseline EDSS and failure of complete relapse suppression were associated with a significantly greater likelihood of accumulation of fixed disability . Multiple Sclerosis 2007 ; 13 : 336 - 342 . Background : In patients with relapsing – remitting multiple sclerosis ( RRMS ) , a scoring system based on new magnetic resonance imaging ( MRI ) active lesions , relapses and sustained disability progression after a 1-year treatment with IFNβ predicted patient disability progression over time ; however , this score had not been tested in patients receiving glatiramer acetate ( GA ) . Objective : The objective of this study was to evaluate whether this previous scoring system can also be applied to patients treated with GA . Methods : This was a prospect i ve , longitudinal study of 151 RRMS patients treated with GA . Their scores were constructed , based on the clinical and MRI activity after 1 year of therapy . Regression analysis was performed , in order to identify the response variables . Results : The total possible score range was 0–3 . Patients with a score of ≥ 2 and those with clinical activity ( with or without MRI activity ) during their first year of treatment were at increased risk of continuing with relapses and /or sustained disability in the next 2 years ( odds ratio ( OR ) : 38.8 ; p < 0.0001 and OR : 7.8 ; p < 0.009 , respectively ) . Conclusions : In RRMS patients treated with GA  , a combination of clinical activity measures may have prognostic value for identifying patients with disease activity in the next 2 years of therapy OBJECTIVE To investigate the value of Exp and ed Disability Status Scale ( EDSS ) worsening sustained for at least 6 months and other parameters as predictors for disability status . DESIGN Retrospective analysis of the Multiple Sclerosis Collaborative Research Group study data . SETTING The intramuscular interferon beta-1a pivotal trial was a double-blind , placebo-controlled phase 3 study . PARTICIPANTS Patients with relapsing-remitting multiple sclerosis who received at least 2 years of treatment and completed an EDSS evaluation 8 years postr and omization . INTERVENTION Thirty micrograms of intramuscular interferon beta-1a or placebo once weekly during the 2-year clinical trial . MAIN OUTCOME MEASURES Positive predictive values for 6-month sustained progression during 2 years were calculated to determine the ability to predict disability status at 8 years . A multivariate logistic regression model was used to assess the relationship between predictors and EDSS milestones at follow-up . RESULTS Forty-five patients had sustained 6-month EDSS progression during the clinical trial and 115 did not . Progression during the trial was the strongest predictor of reaching EDSS milestones at the follow-up visit , 8 years after r and omization . Other independent predictors were treatment arm assignment and baseline EDSS score . CONCLUSION In this phase 3 clinical trial of intramuscular interferon beta-1a , compared with effects of treatment , baseline EDSS score , and number of relapses during the study , worsening of 1 point or more on EDSS from baseline lasting 6 months was the strongest predictor of clinical ly significant disability 8 years after r and omization into the clinical trial BACKGROUND AND PURPOSE To define the predictive value of clinical and magnetic resonance imaging ( MRI ) characteristics in identifying relapsing-remitting multiple sclerosis ( RR-MS ) patients with sustained disability progression during interferon beta ( IFNB ) treatment . METHODS All patients receiving treatment with one of the available IFNB formulations for at least 1 year were included in this single-centre , prospect i ve and post-marketing study . Demographic , clinical and MRI data were collected at IFNB start and at 1 year of therapy ; patients were followed-up at least yearly . Poor clinical response was defined as the occurrence of a sustained disability progression of > or = 1 point in the Exp and ed Disability Status Scale ( EDSS ) during the follow-up period . RESULTS Out of 454 RR-MS patients starting IFNB therapy , data coming from 394 patients with a mean follow-up of 4.8 ( 2.4 ) years were analysed . Sixty patients were excluded because of too short follow-up . Less than 1/3 ( 30.4 % ) of the patients satisfied the criterion of ' poor responders ' . Patients presenting new lesions on T2-weighted MRI scan after 1 year of therapy ( compared with baseline ) had a higher risk of being poor responder to treatment with IFNB during the follow-up period ( HR 16.8 , 95 % CI 7.6 - 37.1 , P < 
    Output:
    
All criteria had a limited predictive value .