***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: In the 12-month phase 3 TRANSFORMS study , fingolimod showed greater efficacy than intramuscular interferon beta (IFNβ)-1a in patients with relapsing – remitting multiple sclerosis ( RRMS ) . This study analyzed fingolimod efficacy compared with IFNβ-1a in patient subgroups from TRANSFORMS . Patients were r and omized to receive fingolimod or weekly IM IFNβ-1a for 12 months . Analyses of efficacy included annualized relapse rate ( ARR ) , and magnetic resonance imaging ( MRI ) measures [ gadolinium (Gd)-enhancing T1 lesions , new/newly enlarged ( active ) T2 lesions , brain volume change ] . Subgroups were defined based on demographics , disease characteristics ( baseline EDSS score , relapse rate , and MRI parameters ) , and response to previous therapy . Fingolimod 0.5 mg reduced ARR over 12 months by 32–59 % relative to IFNβ-1a in all subgroups defined by demographic factors or baseline disease characteristics . Fingolimod also reduced the number of new Gd-enhancing lesions , active T2 lesions , and the rate of brain volume loss , versus IFNβ-1a in most ( 95 % ) subgroups . In patients with high disease activity despite IFNβ treatment in the year before study , fingolimod 0.5 mg reduced ARR by 61 % relative to IFNβ-1a . Reductions in lesion counts and brain volume loss also favored fingolimod in these patients . In conclusion , consistently better efficacy was observed for fingolimod compared with IFNβ-1a across different subgroups of patients with RRMS Objective : To describe detailed MRI results from 2 head-to-head phase III trials , Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I ( CARE-MS I ; NCT00530348 ) and Study II ( CARE-MS II ; NCT00548405 ) , of alemtuzumab vs subcutaneous interferon β-1a ( SC IFN-β-1a ) in patients with active relapsing-remitting multiple sclerosis ( RRMS ) . Methods : The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive ( CARE-MS I ) or who had an inadequate response , defined as at least one relapse , to prior therapy ( CARE-MS II ) . Results : Both treatments prevented T2-hyperintense lesion volume increases from baseline . Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies ( p < 0.05 ) , including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2 . Reduced risk of new T1 lesions ( p < 0.0001 ) and gadolinium-enhancing lesion conversion to T1-hypointense black holes ( p = 0.0078 ) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II . Alemtuzumab  slowed brain volume loss over 2 years in CARE-MS I ( p < 0.0001 ) and II ( p = 0.012 ) vs SC IFN-β-1a . Conclusions : Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS . The superiority of alemtuzumab was more prominent during the second year of both studies . These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS . Clinical Trials.gov identifier : NCT00530348 and NCT00548405 . Classification of evidence : The results reported here provide Class I evidence that , for patients with active RRMS  , alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints Background : Natalizumab and fingolimod were approved for treatment of active relapsing-remitting multiple sclerosis ( RRMS ) in Denmark in 2006 and 2011 , respectively . There have been no r and omized head-to-head studies comparing the two drugs . Objective : To compare the clinical efficacy of natalizumab and fingolimod . Methods : Data on all Danish RRMS patients who started their first second-line treatment with natalizumab or fingolimod from July 2011 to March 2015 were prospect ively recorded in the Danish Multiple Sclerosis ( MS ) Treatment Register . The two treatment arms were 1:1 propensity score matched by baseline covariates using ‘ nearest neighbour ’ method . Results : Propensity score matching left 928 of 1309 RRMS cases , 464 in each treatment group .  The on-treatment annualized relapse rate was 0.296 ( 95 % confidence interval ( CI ) : 0.26–0.34 ) for natalizumab and 0.307 ( 95 % CI : 0.27–0.35 ) for fingolimod . The adjusted relapse rate ratio was 0.93 ( 95 % CI : 0.74–1.17 ; p = 0.53 ) . Mean time to first relapse was 2.55 and 2.56 years , respectively ( p = 0.76 ) . There was no difference in change of Exp and ed Disability Status Scale ( EDSS ) . Conclusion : We found no differences in clinical disease activity  between natalizumab- and fingolimod-treated RRMS patients in this real-life observational study . However , the lack of magnetic resonance imaging ( MRI ) data for the propensity score matching may conceal a higher efficacy of natalizumab Objective : This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis . Methods : Analysis of prospect ively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospect i ve follow-up from the MSBase cohort study . Multivariable linear regression models assessed associations between relapse incidence , phenotype and changes in disability ( quantified with Exp and ed Disability Status Scale and its Functional System scores ) . Sensitivity analyses were conducted . Results : In 34,858 relapses recorded during 136,462 patient-years ( median follow-up 5.9 years ) , higher relapse incidence was associated with greater disability accumulation ( β = 0.16 , p < 0.001 ) . Relapses of all phenotypes promoted disability accumulation , with the most pronounced increase associated with pyramidal ( β = 0.27 ( 0.25–0.29 ) ) , cerebellar ( β = 0.35 ( 0.30–0.39 ) ) and bowel/bladder ( β = 0.42 ( 0.35–0.49 ) ) phenotypes ( mean ( 95 % confidence interval ) ) . Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain , as well as anatomically related domains . Conclusion : Relapses are associated with accumulation of neurological disability . Relapses in pyramidal , cerebellar and bowel/bladder systems have the greatest association with disability change . Therefore , prevention of these relapses is an important objective of disease-modifying therapy . The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis BACKGROUND The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis . We aim ed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment . METHODS In our 2 year , rater-masked , r and omised controlled phase 3 trial , we enrolled adults aged 18 - 55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer . Eligible participants were r and omly allocated in a 1:2:2 ratio by an interactive voice response system , stratified by site , to receive subcutaneous interferon beta 1a 44 μg , intravenous alemtuzumab 12 mg per day , or intravenous alemtuzumab 24 mg per day . Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months . The 24 mg per day group was discontinued to aid recruitment , but data are included for safety assessment s. Co primary endpoints were relapse rate and time to 6 month sustained accumulation of disability , comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00548405 . FINDINGS 202 ( 87 % ) of 231 patients r and omly allocated interferon beta 1a and 426 ( 98 % ) of 436 patients r and omly allocated alemtuzumab 12 mg were included in the primary analyses . 104 ( 51 % ) patients in the interferon beta 1a group relapsed ( 201 events ) compared with 147 ( 35 % ) patients in the alemtuzumab group ( 236 events ; rate ratio 0·51 [ 95 % CI 0·39 - 0·65 ] ; p<0·0001 ) , corresponding to a 49·4 % improvement with alemtuzumab . 94 ( 47 % ) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 ( 65 % ) patients in the alemtuzumab group ( p<0·0001 ) . 40 ( 20 % ) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 ( 13 % ) in the alemtuzumab group ( hazard ratio 0·58 [ 95 % CI 0·38 - 0·87 ] ; p=0·008 ) , corresponding to a 42 % improvement in the alemtuzumab group . For 435 patients allocated alemtuzumab 12 mg , 393 ( 90 % ) had infusion-associated reactions , 334 ( 77 % ) had infections ( compared with 134 [ 66 % ] of 202 patients in the interferon beta 1a group ) that were mostly mild-moderate with none fatal , 69 ( 16 % ) had thyroid disorders , and three ( 1 % ) had immune thrombocytopenia . INTERPRETATION For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis , alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability . Suitable risk management strategies allow for early identification of alemtuzumab 's main adverse effect of secondary autoimmunity . FUNDING Genzyme ( Sanofi ) and Bayer Schering Pharma Objective : To determine the percentage of patients with residual deficits following multiple sclerosis ( MS ) exacerbations and the magnitude of those deficits using a data base of pooled placebo patients from clinical trials . Methods : A data base of patients assigned to the placebo group in several r and omized clinical trials was queried to determine those patients with Exp and ed Disability Status Scale ( EDSS ) and Scripps Neurologic Rating Scale assessment s prior to , at the time of , and after an acute exacerbation of MS . The extent of deficit present at these time points was compared to determine the acute effect of exacerbations and the degree of persistent disability . Results : Forty-two percent of patients had residual deficit of at least 0.5 and 28 % had residual of ≥1.0 EDSS units , at an average of 64 days after an exacerbation . The results were reproduced across subsequent exacerbations and were sustained over time . The subgroup of patients with measurable change in EDSS during the exacerbation had more extensive residual impairment on the follow-up visits . Similar results were seen when the Scripps score was examined . Conclusion : MS exacerbations produce a measurable and sustained effect on disability BACKGROUND Daclizumab , a humanised monoclonal antibody , modulates interleukin-2 signalling by blocking the α subunit ( CD25 ) of the interleukin-2 receptor . We assessed whether daclizumab high-yield process ( HYP ) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis . METHODS We did a r and omised , double-blind , placebo-controlled trial at 76 centres in the Czech Republic , Germany , Hungary , India , Pol and , Russia , Ukraine , Turkey , and the UK between Feb 15 , 2008 , and May 14 , 2010 . Patients aged 18 - 55 years with relapsing-remitting multiple sclerosis were r and omly assigned ( 1:1:1 ) , via a central interactive voice response system , to subcutaneous injections of daclizumab HYP 150 mg or 300 mg , or placebo , every 4 weeks for 52 weeks . Patients and study personnel were mask 
    Output:
    
The literature suggests that treatment with high-efficacy immunotherapies is more potent in suppressing relapse activity when initiated early vs. with a delay after the MS diagnosis .