***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: Introduction Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis ( MS ) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents . In this study , we evaluate the rate of cerebral atrophy in a 6-month period , investigate the predictive and explanatory value of other magnetic resonance imaging ( MRI ) measures in relation to cerebral atrophy , and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure . Methods One hundred thirty-five relapsing – remitting multiple sclerosis patients underwent six monthly MRI scans  from which the percentage brain volume change ( PBVC ) and the number and volume of gadolinium (Gd)-enhancing lesions , T2 lesions , and persistent black holes ( PBH ) were determined . By means of multiple linear regression analysis , the relationship between focal MRI variables and PBVC was assessed . Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline . Results A significant atrophy occurred over 6 months ( PBVC = −0.33 % , SE = 0.061 , p < 0.0001 ) . The number of baseline T2 lesions ( p = 0.024 ) , the on- study Gd-enhancing lesion volume ( p = 0.044 ) , and the number of on- study PBHs ( p = 0.003 ) were associated with an increased rate of atrophy . For a 50 % decrease in rate of atrophy , the sample size calculations showed that approximately 283 patients per arm are required in an unselected sample d population and 185 patients per arm are required in a selected population . Conclusion Within a 6-month period , significant atrophy can be detected and on- study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism . Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power Background : Laquinimod is a novel immunomodulatory substance developed as an orally available disease modifying treatment in multiple sclerosis ( MS ) . The purpose of this study was to evaluate safety , tolerability , and efficacy on MRI lesions of two different doses of laquinimod compared with placebo in patients with relapsing MS . Methods : In this multicenter , double-blind , r and omized trial , patients with relapsing MS received 0.1 mg or 0.3 mg laquinimod or placebo as three daily tablets for 24 weeks . Gadolinium-enhanced brain MRI scans were performed at screening , every eighth week during treatment , and 8 weeks after end of treatment . The primary efficacy variable was the cumulative number of active lesions over 24 weeks . Safety measures included adverse events , physical examination , and laboratory variables . Results : Of 256 screened patients , 209 were r and omized ( 67 to 74 patients per group ) in 20 centers . There was a significant difference between laquinimod 0.3 mg and placebo for the primary outcome measure ( mean cumulative number of active lesions reduced by 44 % ) . In the subgroup of patients with at least one active lesion at baseline the reduction was slightly more pronounced ( 52 % ) . No differences with respect to clinical variables ( relapses , disability ) were found . The safety profile was favorable ; there were no clinical signs of undesired inflammatory manifestations . Conclusion : Oral laquinimod in a dosage of 0.3 mg daily was well tolerated and effective in suppressing development of active lesions in relapsing multiple sclerosis Multiple sclerosis ( MS ) has serious negative effects on health- , social- , and work-related issues for the patients and their families , thus causing significant socioeconomic burden . The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national sample . We used all national records from the Danish National Patient Registry ( 1998 - 2006 ) , and identified 10,849 MS patients which were compared with 43,396 r and omly age- , sex- and social matched citizens .  Healthcare sector costs included frequencies and costs of hospitalizations and weighted outpatient use , frequencies of visits and hospitalizations and costs from primary sectors , and the use and costs of drugs . Productivity costs ( the value of lost productivity from time off from work due to illness ) and all social transfer payments were also calculated . Patients with MS had significantly higher rates of health-related contact and medication use and very low employment rate which incurred a higher socioeconomic cost . The income level of employed MS patients was significantly lower than that of control subjects . The annual total health sector costs and productivity costs were € 14,575 for MS patients vs. € 1163 for control subjects ( p<0.001 ) , corresponding to an annual mean excess health-related cost of € 13,413 for each patient with MS . In addition , the MS patients received an annual mean excess social transfer income of € 6843 . MS present social and economical consequences more than eight years before diagnosis . We conclude that MS causes major socioeconomic consequences for the individual patient and for society . Productivity costs are a far more important economic factor , especially due to reduced employment , which are enhanced by the early age of diagnose onset CONTEXT Interferon beta is widely prescribed to treat multiple sclerosis ( MS ) ; however , its relationship with disability progression has yet to be established . OBJECTIVE To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS . DESIGN , SETTING , AND PATIENTS Retrospective cohort study based on prospect ively collected data ( 1985 - 2008 ) from British Columbia , Canada . Patients with relapsing-remitting MS treated with interferon beta ( n = 868 ) were compared with untreated contemporary ( n = 829 ) and historical ( n = 959 ) cohorts . MAIN OUTCOME MEASURES The main outcome measure was time from interferon beta treatment eligibility ( baseline ) to a confirmed and sustained score of 6 ( requiring a cane to walk 100 m ; confirmed at > 150 days with no measurable improvement ) on the Exp and ed Disability Status Scale ( EDSS ) ( range , 0 - 10 , with higher scores indicating higher disability ) . A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment . Analyses also included propensity score adjustment to address confounding by indication . RESULTS The median active follow-up times ( first to last EDSS measurement ) were as follows : for the interferon beta-treated cohort , 5.1 years ( interquartile range [ IQR ] , 3.0 - 7.0 years ) ; for the contemporary control cohort , 4.0 years ( IQR , 2.1 - 6.4 years ) ; and for the historical control cohort , 10.8 years ( IQR , 6.3 - 14.7 years ) . The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8 % , 5.3 % , and 23.1 % in the 3 cohorts , respectively . After adjustment for potential baseline confounders ( sex , age , disease duration , and EDSS score ) , exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort ( hazard ratio , 1.30 ; 95 % CI , 0.92 - 1.83 ; P = .14 ) or the historical control cohort ( hazard ratio , 0.77 ; 95 % CI , 0.58 - 1.02 ; P = .07 ) were considered . Further adjustment for comorbidities and socioeconomic status , where possible , did not change interpretations , and propensity score adjustment did not substantially change the results . CONCLUSION Among patients with relapsing-remitting MS , administration of interferon beta was not associated with a reduction in progression of disability BACKGROUND A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions . We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind , placebo-controlled phase IIb study . METHODS The study was done in 51 centres in nine countries . Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing ( GdE ) lesion on screening MRI . Of 720 patients screened , 306 eligible patients were enrolled . Patients , aged 18 - 50 years , were r and omly assigned to placebo ( n=102 ) , laquinimod 0.3 mg a day ( n=98 ) , or 0.6 mg a day ( n=106 ) . Brain MRI scans and clinical assessment s were done at week -4 , baseline , and monthly from week 12 to week 36 . The primary outcome was the cumulative number of GdE lesions at weeks 24 , 28 , 32 , and 36 . The principal analysis of the primary endpoint was done on the intention-to-treat cohort . This study is registered with Clinical Trials.gov , number NCT00349193 . FINDINGS Compared with placebo , treatment with laquinimod 0.6 mg per day showed a 40.4 % reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans ( simple means 4.2 [ SD 9.2 ] vs 2.6 [ 5.3 ] , p=0.0048 ) ; treatment with 0.3 mg per day showed no significant effects ( 3.9 [ 5.5 ] vs placebo , p=0.6740 ) . Both doses of laquinimod were well tolerated , with some transient and dose-dependent increases in liver enzymes . A case of Budd-Chiari syndrome-ie , a thrombotic venous outflow obstruction of the liver-occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0.6 mg laquinimod . Anticoagulant treatment result ed in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation . INTERPRETATION In patients with relapsing-remitting multiple sclerosis , 0.6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated The aim of this study was to determine evolution of T1 unenhanced hypointense lesions ( acute or chronic black holes ( ABHs , CBHs ) ) by measuring their magnetization transfer ratio ( MTR ) changes over 12 months .  40 glatiramer acetate (GA)-naive patients with relapsing-remitting MS who presented with 1 or more contrast-enhancing lesions ( CELs ) at baseline underwent 1.5-T MRI at baseline and after 12 months . Lesions were classified into 4 patterns based on differences in lesion isointensity or hypointensity over 12 months . Of 115 CELs detected at baseline , 64 , after 12 months , followed pattern A ( isointense-isointense ) , 6 pattern B ( isointense-hypointense ) , 33 pattern C ( hypointense-isointense ) , and 12 pattern D ( hypointense-hypointense ) . MTR significantly increased for all unenhanced T1 hypointense lesions ( p = 0.02 ) . Highest MTR increases were observed for patterns C ( ABHs + 18.2 % , p less than 0.001 ) and D ( CBHs + 34.2 % , p = 0.023 ) , but significant improvement was also detected for pattern A ( + 1.4 % , p = 0.046 ) ; no significant MTR changes were found for pattern B. GA treatment significantly recovered MTR in ABHs and CBHs , possibly indicating a greater potential for remyelination Background : Laquinimod , an oral novel immunomodulator , was shown to reduce MRI-measured disease activity in relapsing — remitting MS ( RRMS ) patients . Objectives : To determine whether the safety and efficacy profile of laquinimod , as shown in a placebo-controlled 36-week trial ( LAQ/5062 ) , is sustained and reproducible . Methods : Two hundred and fifty seven patients entered the extension phase in which MRI  was performed at the beginning and at the end of the active extension phase . Clinical assessment s were performed at weeks 4 , 12 and every 12 weeks thereafter . Results : Two hundred and thirty nine ( 93 % ) patients completed the extension phase and 222 ( 86.3 % ) had a final scan available .  Gadolinium-enhanced ( GdE ) T1 lesions were significantly reduced for patients switching from placebo to 0.3/ 0.6 mg doses ( 52 % , p = 0.0006 ) . In patients initially r and omized to 0.6 mg in LAQ/5062 the reduction of MRI activity observed in the placebo-controlled phase was maintained in the extension . The proportion of GdE-free patients for those who switched from placebo increased from a baseline of 31 % to 47 % at the end of the extension phase ( p = 0.01 ) . The most prominent safety signal was elevations of liver enzymes , reversible in all cases . Conclusions : The good efficacy and the excellent safety and tolerability profiles of laquinimod 0.6 mg/day are confirmed in this extension study BACKGROUND Two proof-of-concept clinical 
    Output:
    
Laquinimod had potential benefits in reducing relapse rates and was safe for most patients with RRMS in the short term .
The published study suggests that laquinimod at a dose of 0.6 mg orally administered once daily may be safe and have potential benefits for most patients with RRMS in the short term .