***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 performed yearly MRI analyses on 327 of the total 372 patients in a multicenter , r and omized , double-blind , placebo-controlled trial of interferon beta-1b ( IFNB ) .  Clinical results are presented in the preceding companion paper . Baseline MRI characteristics were the same in all treatment groups . Fifty-two patients at one center formed a cohort for frequent MRIs ( one every 6 weeks ) for analysis of disease activity . The MRI results support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans ( median 80 % reduction , p = 0.0082 ) and appearance of new lesions . In addition , there was an equally significant reduction in MRI-detected burden of disease in the treatment as compared with placebo groups ( mean group difference of 23 % , p = 0.001 ) . These results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients 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 OBJECTIVE To study changes in brain volume measured monthly in patients treated for relapsing multiple sclerosis due to loss of tissue and the appearance of inflammation . DESIGN AND PATIENTS The results from T2/fluid-attenuated inversion recovery axial images from 13 consecutive monthly 3-T brain magnetic resonance imaging tests conducted on 74 patients diagnosed with relapsing multiple sclerosis in the BECOME study were used to calculate whole brain volumes using automated software analysis tools . The patients had been r and omized to receive treatment with interferon beta-1b or glatiramer acetate .  Ongoing inflammation was studied by counting the number of combined active lesions and measuring the volume of gadolinium enhancement . A mixed-effects model was used to analyze brain volumes over time . RESULTS There was a significant decrease in brain volume over time but there was no difference in its rate of change by age , sex , frequency of ongoing inflammation , multiple sclerosis type , or r and omized treatment assignment . The mean rate of brain volume change per month from multivariable models was -1.1 cm(3 ) ( 95 % CI , -1.5 to -0.6 ) and during times of magnetic resonance imaging activity , it increased transiently by an average of 1.2 cm(3)/lesion ( 95 % CI , 0.7 to 1.7 ) and 7.1 cm(3)/1 cm(3 ) of gadolinium volume . In a model with both measures , combined active lesions were independent predictors of brain volume but gadolinium volume was not . CONCLUSION Two major changes in brain volume occur in patients with relapsing multiple sclerosis , a steady decrease likely due to tissue loss with overlapping transient increases due to the appearance of inflammation Objective : To measure the effects of disease-modifying drugs ( DMDs ) on the development of cortical lesions ( CL ) and cortical atrophy in patients with relapsing – remitting multiple sclerosis ( RRMS ) . Methods : RRMS patients ( n = 165 ) were r and omized to subcutaneous ( sc ) interferon ( IFN ) beta-1a ( 44 mcg three times weekly ) , intramuscular ( i m ) IFN beta-1a ( 30 mcg weekly ) or glatiramer acetate ( GA ; 20 mg daily ) . The reference population comprised 50 untreated patients .  Clinical and MRI examinations were performed at baseline , 12 months and 24 months . Results : One hundred and forty-one treated patients completed the study . After 12 months , 37/50 ( 74 % ) of untreated patients developed ≥1 new CL ( mean 1.6 ) , compared with 30/47 ( 64 % ) of i m IFN beta-1a-treated patients ( mean 1.2 , p = 0.021 ) , 24/48 ( 50 % ) of GA-treated patients ( mean 0.8 , p = 0.001 ) and 12/46 ( 26 % ) of sc IFN beta-1a-treated patients ( mean 0.4 , p < 0.001 ) . After 24 months , ≥1 new CL was observed in 41/50 ( 82 % ) of untreated ( mean 3.0 ) , 34/47 ( 72 % ) of i m IFN beta-1a-treated ( mean 1.6 , p < 0.001 ) , 30/48 ( 62 % ) of GA-treated ( mean 1.3 , p < 0.001 ) and 24/46 ( 52 % ) of sc IFN beta-1a-treated patients ( mean 0.8 , p < 0.001 ) . Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients ( p = 0.023 ) . Conclusions : Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients , with faster and more pronounced effects seen with sc IFN beta-1a than with i m IFN beta-1a or GA Evidence of a significant improvement of IFNB-1b in clinical severity in the older population with RRMS has not been established so far . The aim of this exploratory post hoc analysis of the 250 mcg IFNB-1b group of the BEYOND study is to compare the efficacy and safety of older versus younger patients using a cut-off at the age of 50 and at the age of 40 , respectively . There was no difference between age groups in adjusted relapse risk ( age 50 cut-off : P = 0.482 , age 40 cut-off : P = 0.073 ) nor in adjusted time to confirmed EDSS progression ( age 50 cut-off : P = 0.096 , age 40 cut-off : P = 0.189 ) . There were no significant differences between patients < 50 and ≥50 years in the adjusted annualized relapse rate ( P = 0.285 ) , whereas relapse rate was higher in the < 40 as compared to the ≥40 group ( P = 0.024 ) . The proportion of patients with confirmed disability progression was not significantly different for the 50 cutoff ( P = 0.148 ) , whereas significantly fewer < 40 than ≥40 patients had disability progression ( P = 0.047 ) . Only minor differences in adverse event frequencies between the age groups for the two cut-offs were seen . These results indicate that IFNB-1b  is as efficacious and safe in patients ≥50 years as < 50 years of age To evaluate the safety , tolerability , and efficacy of glatiramer acetate ( GA ) 40 mg compared to a 20 mg dose Switching treatment may be beneficial in patients with relapsing – remitting multiple sclerosis ( RRMS ) who respond inadequately to first‐line immunomodulatory therapy . The objective of this study was to evaluate clinical outcomes after switching treatment in such patients . This prospect i ve longitudinal observational study included 114 patients with RRMS who failed first‐line monotherapy and were switched treatments after 3 years . Every 3 months , patients underwent a full neurological examination . Outcome was compared between the 3‐year Before Switch and After Switch treatment periods . The primary outcome measure was the annualized relapse rate ; secondary outcome measures were the proportion of relapse‐free patients and the median change in Exp and ed Disability Status Scale ( EDSS ) . Patients were switched either from low‐dose to high‐dose interferon‐β ( IFNβ ; n = 31 ) , from IFNβ to glatiramer acetate ( GA ; n = 52 ) or mitoxantrone ( n = 13 ) , or from GA to IFNβ ( n = 16 ) . In 3 years after switching , annualized relapse rates fell by 57–78 % according to the group . The proportion of relapse‐free patients varied from 56 % to 81 % . Least improved was observed in patients switching between INFβ preparations . Median EDSS scores remained stable in all groups except the GA to IFNβ switchers . In conclusion , patients who fail first‐line immunomodulatory therapy generally benefit from switching to another class of immunomodulatory therapy BACKGROUND Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis ( RRMS ) , but no published r and omised trials have directly compared these two drugs . Our aim in the REGARD ( REbif vs Glatiramer Acetate in Relapsing MS Disease ) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS . METHODS In this multicentre , r and omised , comparative , parallel-group , open-label study , patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were r and omised to receive 44 mug subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse . A sub population of 460 patients ( 230 from each group ) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume . Treatments were assigned by a computer-generated r and omisation list that was stratified by centre . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00078338 . FINDINGS Between February and December , 2004 , 764 patients were r and omly assigned : 386 to interferon beta-1a and 378 to glatiramer acetate . After 96 weeks , there was no significant difference between groups in time to first relapse ( hazard ratio 0.94 , 95 % CI 0.74 to 1.21 ; p=0.64 ) . Relapse rates were lower than expected : 258 patients ( 126 in the interferon beta-1a group and 132 in the glatiramer acetate group ) had one or more relapses ( the expected number was 460 ) . For secondary outcomes , there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions , although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions ( 0.24 vs 0.41 lesions per patient per scan , 95 % CI -0.4 to 0.1 ; p=0.0002 ) . Safety and tolerability profiles were consistent with the known profiles for both compounds . The overall number and severity of adverse events were similar between 
    Output:
    
The effects of IFNs-beta and GA in the treatment of people with RRMS , including clinical ( e.g. people with relapse , risk to progression ) and MRI ( Gd-enhancing lesions ) measures , seem to be similar or to show only small differences .
When MRI lesion load accrual is considered , the effect of the two treatments differs , in that IFNs-beta were found to limit the increase in lesion burden as compared with GA .
Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes , such as quality -of-life measures