***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: We compared the relative efficacy of interferon beta ( IFNβ ) products and azathioprine ( AZA ) in the treatment of relapsing- remitting multiple sclerosis ( RRMS ) . Ninety-four previously untreated patients of short duration with RRMS were r and omly allocated to the two treatment groups . The first group received IFNβ products ( Betaferon , Avonex or Rebif ) ; the second group received AZA for 12 months .  Response to treatment was assessed at 3 , 6 , and 12 months after starting therapy . The mean number of relapse during one year of the study was lower in the AZA group than in the IFNβ products group ( 0.28 vs. 0.64 , P < 0.05).After 12 months , 57.4 % of patients receiving IFNβ products remained relapse free compared with 76.6 % of those given AZA . The Exp and ed Disability Status Scale ( EDSS ) decreased by 0.30 units in IFNβ-treated patients ( P < 0.05 ) and 0.46 in AZAtreated patients ( P < 0.001 ) . Treatment with IFNβ products and AZA  significantly reduces the relapse rate and EDSS score in patients with RRMS , while AZA is more effective than the IFNβ formulations BACKGROUND Fingolimod has shown reductions in clinical and MRI disease activity in patients with relapsing-remitting multiple sclerosis . We further assessed the efficacy and safety of fingolimod in such patients . METHODS We did this placebo-controlled , double-blind phase 3 study predominantly in the USA ( 101 of 117 centres ) . Using a computer-generated sequence , we r and omly allocated eligible patients -those aged 18 - 55 years with relapsing-remitting multiple sclerosis-to  receive fingolimod 0·5 mg , fingolimod 1·25 mg , or placebo orally once daily ( 1:1:1 ; stratified by study centre ) . On Nov 12 , 2009 , all patients assigned to fingolimod 1·25 mg were switched to the 0·5 mg dose in a blinded manner after a review of data from other phase 3 trials and recommendation from the data and safety monitoring board , but were analysed as being in the 1·25 mg group in the primary outcome analysis . Our primary endpoint was annualised relapse rate at month 24 , analysed by intention to treat . Secondary endpoints included percentage brain volume change ( PBVC ) from baseline and time-to-disability-progression confirmed at 3 months . This trial is registered with Clinical Trilals.gov , number NCT00355134 . FINDINGS Between June 30 , 2006 , and March 4 , 2009 , we enrolled and r and omly allocated 1083 patients : 370 to fingolimod 1·25 mg , 358 to fingolimod 0·5 mg , and 355 to placebo  . Mean annualised relapse rate was 0·40 ( 95 % CI 0·34 - 0·48 ) in patients given placebo and 0·21 ( 0·17 - 0·25 ) in patients given fingolimod 0·5 mg : rate ratio 0·52 ( 95 % CI 0·40 - 0·66 ; p<0·0001 ) , corresponding to a reduction of 48 % with fingolimod 0·5 mg versus placebo . Mean PBVC was -0·86 ( SD 1·22 ) for fingolimod 0·5 mg versus -1·28 ( 1·50 ) for placebo ( treatment difference -0·41 , 95 % CI -0·62 to -0·20 ; p=0·0002 ) . We recorded no statistically significant between-group difference in confirmed disability progression ( hazard rate 0·83 with fingolimod 0·5 mg vs placebo ; 95 % CI 0·61 - 1·12 ; p=0·227 ) . Fingolimod 0·5 mg caused more of the following adverse events versus placebo : lymphopenia ( 27 [ 8 % ] patients vs 0 patients ) , increased alanine aminotransferase ( 29 [ 8 % ] vs six [ 2 % ] ) , herpes zoster infection ( nine [ 3 % ] vs three [ 1 % ] ) , hypertension ( 32 [ 9 % ] vs 11 [ 3 % ] ) , first-dose bradycardia ( five [ 1 % ] vs one [ < 0·5 % ] ) , and first-degree atrioventricular block ( 17 [ 5 % ] vs seven [ 2 % ] ) . 53 ( 15 % ) of 358 patients given fingolimod 0·5 mg and 45 ( 13 % ) of 355 patients given placebo had serious adverse events over 24 months , which included basal-cell carcinoma ( ten [ 3 % ] patients vs two [ 1 % ] patients ) , macular oedema ( three [ 1 % ] vs two [ 1 % ] ) , infections ( 11 [ 3 % ] vs four [ 1 % ] ) , and neoplasms ( 13 [ 4 % ] vs eight [ 2 % ] ) . INTERPRETATION Our findings exp and knowledge of the safety profile of fingolimod and strengthen evidence for its beneficial effects on relapse rates in patients with relapsing-remitting multiple sclerosis . We saw no effect of fingolimod on disability progression . Our findings substantiate the beneficial profile of fingolimod as a disease-modifying agent in the management of patients with relapsing-remitting multiple sclerosis . FUNDING Novartis Pharma AG BACKGROUND BG-12 ( dimethyl fumarate ) is in development as an oral treatment for  relapsing-remitting multiple sclerosis  , which is commonly treated with parenteral agents ( interferon or glatiramer acetate ) . METHODS In this phase 3 , r and omized study , we investigated the efficacy and safety of oral BG-12 , at a dose of 240 mg two or three times daily , as compared with placebo in patients with relapsing-remitting multiple sclerosis . An active agent , glatiramer acetate , was also included as a reference comparator . The primary end point was the annualized relapse rate over a period of 2 years . The study was not design ed to test the superiority or noninferiority of BG-12 versus glatiramer acetate . RESULTS At 2 years , the annualized relapse rate was significantly lower with twice-daily BG-12 ( 0.22 ) , thrice-daily BG-12 ( 0.20 ) , and glatiramer acetate ( 0.29 ) than with placebo ( 0.40 ) ( relative reductions : twice-daily BG-12 , 44 % , P<0.001 ; thrice-daily BG-12 , 51 % , P<0.001 ; glatiramer acetate , 29 % , P=0.01 ) . Reductions in disability progression with twice-daily BG-12 , thrice-daily BG-12 , and glatiramer acetate versus placebo ( 21 % , 24 % , and 7 % , respectively ) were not significant . As compared with placebo , twice-daily BG-12 , thrice-daily BG-12 , and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions ( all P<0.001 ) and new T(1)-weighted hypointense lesions ( P<0.001 , P<0.001 , and P=0.002 , respectively ) . In post hoc comparisons of BG-12 versus glatiramer acetate , differences were not significant except for the annualized relapse rate ( thrice-daily BG-12 ) , new or enlarging T(2)-weighted hyperintense lesions ( both BG-12 doses ) , and new T(1)-weighted hypointense lesions ( thrice-daily BG-12 ) ( nominal P<0.05 for each comparison ) . Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events ( with BG-12 ) and injection-related events ( with glatiramer acetate ) . There were no malignant neoplasms or opportunistic infections reported with BG-12 . Lymphocyte counts decreased with BG-12 . CONCLUSIONS In patients with relapsing-remitting multiple sclerosis , BG-12 ( at both doses ) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo . ( Funded by Biogen Idec ; CONFIRM Clinical Trials.gov number , NCT00451451 . ) BACKGROUND Interleukin 12 ( IL-12 ) , a cytokine that promotes generation of helper T cells subtype 1 , is increased in multiple sclerosis . Albuterol sulfate , a β2-adrenergic agonist , reduces IL-12 expression , so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy . OBJECTIVES To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment . DESIGN Single-center double-masked clinical trial . SETTING Academic research . Patients Subjects with relapsing-remitting multiple sclerosis . MAIN OUTCOME MEASURES In this single-center double-masked clinical trial , subjects with relapsing-remitting multiple sclerosis were r and omized to receive a subcutaneous injection of glatiramer acetate ( 20 mg ) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate ( 20 mg ) plus an oral dose of albuterol daily for 2 years . The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years , and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point . The classification level of evidence from this trial is C for each question , as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol . RESULTS Forty-four subjects were r and omized to  receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo , and 39 subjects contributed to the analysis  . Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month ( P = .005 ) and 12-month ( P = .04 ) time points but not at the 24-month time point . A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group ( P = .03 ) . Immunologically , IL-13 and interferon-γ production decreased in both treatment groups , and a treatment effect on IL-13 production was observed at the 12-month time point ( P < .05 ) . Adverse events were generally mild , and only 3 moderate or severe events were considered related to the treatment . CONCLUSION Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00039988 A double‐blind , r and omized , controlled study was undertaken to determine whether combined use of interferon β‐1a ( IFN ) 30μg intramuscularly weekly and glatiramer acetate ( GA ) 20 mg daily is more efficacious than either agent alone in relapsing – remitting 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 
    Output:
    
Our review shows that alemtuzumab , natalizumab , and fingolimod are the best choices for preventing clinical relapses in people with RRMS , but this evidence is limited to the first 24 months of follow-up .
For the prevention of disability worsening in the short term ( 24 months ) , only natalizumab shows a beneficial effect on the basis of moderate quality evidence ( all of the other estimates were based on low to very low quality evidence ) .
Currently , therefore , insufficient evidence is available to evaluate treatments for the prevention of irreversible disability worsening .