***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: 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 BG-12 ( dimethyl fumarate ) was shown to have antiinflammatory and cytoprotective properties in pre clinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging ( MRI ) in a phase 2 , placebo-controlled study involving patients with relapsing-remitting multiple sclerosis . METHODS We conducted a r and omized , double-blind , placebo-controlled phase 3 study involving patients with relapsing-remitting multiple sclerosis . Patients were r and omly assigned to receive oral BG-12 at a dose of 240 mg twice daily , BG-12 at a dose of 240 mg three times daily , or placebo . The primary end point was the proportion of patients who had a relapse by 2 years . Other end points included the annualized relapse rate , the time to confirmed progression of disability , and findings on MRI . RESULTS The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group ( 27 % with BG-12 twice daily and 26 % with BG-12 thrice daily vs. 46 % with placebo , P<0.001 for both comparisons ) . The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group , as compared with 0.36 in the placebo group , representing relative reductions of 53 % and 48 % with the two BG-12 regimens , respectively ( P<0.001 for the comparison of each BG-12 regimen with placebo ) . The estimated proportion of patients with confirmed progression of disability was 16 % in the twice-daily BG-12 group , 18 % in the thrice-daily BG-12 group , and 27 % in the placebo group , with significant relative risk reductions of 38 % with BG-12 twice daily ( P=0.005 ) and 34 % with BG-12 thrice daily ( P=0.01 ) . BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted hyperintense lesions ( P<0.001 for the comparison of each BG-12 regimen with placebo ) . Adverse events associated with BG-12 included flushing and gastrointestinal events , such as diarrhea , nausea , and upper abdominal pain , as well as decreased lymphocyte counts and elevated liver aminotransferase levels . CONCLUSIONS In patients with relapsing-remitting multiple sclerosis , both BG-12 regimens , as compared with placebo , significantly reduced the proportion of patients who had a relapse , the annualized relapse rate , the rate of disability progression , and the number of lesions on MRI . ( Funded by Biogen Idec ; DEFINE Clinical Trials.gov number , NCT00420212 . ) Background : Oral BG-12 ( dimethyl fumarate ) , approved for the treatment of the relapsing forms of MS , has demonstrated clinical efficacy with an acceptable safety profile in the Phase III “ Determination of the Efficacy and Safety of Oral Fumarate in Relapsing – Remitting Multiple Sclerosis ( RRMS ) ” ( DEFINE ) and “ Comparator and an Oral Fumarate in RRMS ” ( CONFIRM ) studies . Objectives : To evaluate the health-related quality of life ( HRQoL ) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study . Methods : Patients with RRMS were r and omized to BG-12 240 mg twice ( BID ) or three times ( TID ) daily , or placebo , for 2 years . HRQoL was assessed by the Short Form-36 ( SF-36 ) , global assessment of well-being visual analog scale and the EuroQol-5D . Results : In the 1237 patients from DEFINE , HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse . Change in SF-36 physical component summary scores during 2 years ’ treatment significantly favored BG-12 over placebo ( both doses : p < 0.001 ) . We saw similar benefits in other measures of functioning and general well-being as early as Week 24 . These benefits were maintained during the study . Conclusions : Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures , which coupled with significant clinical efficacy , further support its use as a new treatment for RRMS In the double-blind , placebo-controlled , Phase 3 DEFINE study in patients with relapsing – remitting multiple sclerosis ,  oral BG-12 ( dimethyl fumarate ) significantly reduced the proportion of patients relapsed ( primary endpoint ) , the annualized relapse rate ( ARR ) , and confirmed disability progression ( secondary endpoints ) at two years compared with placebo . We investigated the efficacy of BG-12 240 mg twice daily ( BID ) and three times daily ( TID ) in patient subgroups stratified according to baseline demographic and disease characteristics including gender , age , relapse history , McDonald criteria , treatment history , exp and ed disability status scale score , T2 lesion volume , and gadolinium-enhancing lesions . The clinical efficacy of BG-12 was generally consistent across patient subgroups and reflected positive findings in the overall DEFINE study population . Treatment with BG-12 BID and TID reduced the proportion of patients relapsed and the ARR at two years compared with placebo in all patient subgroups . Reductions in the risk of relapse with BG-12 BID vs. placebo ranged from 68 % [ hazard ratio 0.32 ( 95 % confidence interval ( CI ) 0.16–0.62 ) ] to 26 % [ 0.74 ( 0.51–1.09 ) ] and from 66 % [ 0.34 ( 0.23–0.50 ) ] to 25 % [ 0.75 ( 0.42–1.36 ) ] with BG-12 TID vs. placebo . BG-12 also reduced the risk of disability progression at two years compared with placebo in most subgroups of patients treated with the BID dosing regimen and in all subgroups treated with the TID regimen . These analyses indicate that treatment with BG-12 is consistently effective across a wide spectrum of patients with relapsing – remitting multiple sclerosis with varied demographic and disease characteristics BG-12 , an immunomodulatory agent , reduces frequency of new gadolinium-enhancing ( Gd+ ) lesions in relapsing multiple sclerosis ( MS ) . This study reports the effect of 240 mg BG-12 orally three times daily ( tid ) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions . Brain magnetic resonance imaging ( MRI ) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively . Included patients had at least one new Gd+ lesion from weeks 4 to 12 . Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions .  Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis . The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group . The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34 % lower with BG-12 treatment versus placebo ( 29 % , BG-12 ; 44 % , placebo ; odds ratio 0.51 ; 95 % confidence interval 0.43 , 0.61 ; p < 0.0001 ) . In addition to reducing frequency of new Gd+ lesions , BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo In the phase 3 , r and omized , placebo-controlled and active reference ( glatiramer acetate ) comparator CONFIRM study in patients with relapsing – remitting multiple sclerosis , oral BG-12 ( dimethyl fumarate ) reduced the annualized relapse rate ( ARR ; primary endpoint ) , as well as the proportion of patients relapsed , magnetic resonance imaging lesion activity , and confirmed disability progression , compared with placebo . We investigated the clinical efficacy of BG-12 240 mg twice daily ( BID ) and three times daily ( TID ) in patient subgroups stratified according to baseline demographic and disease characteristics including gender , age , relapse history , McDonald criteria , treatment history , Exp and ed Disability Status Scale score , T2 lesion volume , and gadolinium-enhancing lesions .  BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups , reflecting the positive findings in the overall CONFIRM study population . Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed . Reductions in ARR with BG-12 BID versus placebo ranged from 34 % [ rate ratio 0.664 ( 95 % confidence interval 0.422–1.043 ) ] to 53 % [ 0.466 ( 0.313–0.694 ) ] and from 13 % [ 0.870 ( 0.551–1.373 ) ] to 67 % [ 0.334 ( 0.226–0.493 ) ] with BG-12 TID versus placebo . Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups . The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing – remitting multiple sclerosis with varied demographic and disease characteristics BACKGROUND Oral fumarate ( BG00012 ) might have dual anti-inflammatory and neuroprotective effects . Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing- 
    Output:
    
The overall results of the meta- analysis showed that BG-12 ( at both dosages ) given to patients with RRMS  is safe and statistically significantly more effective than placebo in reducing the proportion of patients who had a relapse by 2 years , the rate of disability progression and the mean number of gadolinium-enhancing lesions at 2 years .
The comparison between BG-12 and glatiramer acetate revealed that the analyzed agent could potentially be more effective in the treatment of RRMS .
Despite limited RCTs data available , both analyzed BG-12 regimens showed their efficacy on clinical disease parameters and other measures of disease activity in RRMS .
The safety profile of the study agent was acceptable