***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 Objective : Interferon ( IFN ) beta has repeatedly shown benefit in multiple sclerosis ( MS ) in reducing the rate of relapse , the disease activity as shown with magnetic resonance imaging and , to some degree , the progression of disability ; however , it is unknown how much the therapeutic response depends on the dose , the subgroup involved , and the disease stage . This multicentre , double blind , placebo controlled study explored the dose−response curve by examining the clinical benefit of low dose IFN beta-1a ( Rebif ® ) , 22 μg subcutaneously once weekly , in patients with secondary progressive MS . Methods : A total of 371 patients with clinical ly definite SPMS were r and omised to receive either placebo or subcutaneous IFN beta-1a , 22 μg once weekly , for 3 years . Clinical assessment s were performed every 6 months . The primary outcome was time to sustained disability , as defined by time to first confirmed 1.0 point increase on the Exp and ed Disability Status Scale ( EDSS ) . Secondary outcomes included a sensitive disability measure and relapse rate . Results : Treatment had no beneficial effect on time to confirmed progression on either the EDSS ( hazard ratio ( HR ) = 1.13 ; 95 % confidence interval ( CI ) 0.82 to 1.57 ; p = 0.45 for 22 μg v placebo ) or the Regional Functional Status Scale ( HR = 0.93 ; 95 % CI 0.68 to 1.28 ; p = 0.67 ) . Other disability measures were also not significantly affected by treatment . Annual relapse rate was 0.27 with placebo and 0.25 with IFN ( rate ratio = 0.90 ; 95 % CI 0.64 to 1.27 ; p = 0.55 ) . The drug was well tolerated with no new safety concerns identified . No significant gender differences were noted . Conclusions : This patient population was less clinical ly active than SPMS population s studied in other trials . Treatment with low dose , IFN beta-1a ( Rebif ® ) once weekly did not show any benefit in this study for either disability or relapse outcomes , including a subgroup with preceding relapses . These results add a point at one extreme of the dose−response spectrum of IFN beta therapy in MS , indicating that relapses in this phase may need treatment with higher doses than in the initial phases Objective : To evaluate the efficacy and safety of interferon beta-1b ( IFNβ-1b ) in subjects with secondary progressive multiple sclerosis ( SPMS ) . Methods : This 3-year , multicenter , double-blind , placebo-controlled , r and omized trial of IFNβ-1b included 939 subjects from the United States and Canada with SPMS and Exp and ed Disability Status Scale ( EDSS ) scores ranging from 3.0 to 6.5 . Subjects were r and omly assigned to receive either placebo or IFNβ-1b ( 250 μg or 160 μg/m2 body surface area ) , administered subcutaneously every other day . The primary outcome was time to progression by ≥1.0 EDSS point ( 0.5 point if EDSS score was 6.0 to 6.5 at entry ) confirmed at 6 months . Secondary outcomes included mean change in EDSS score from baseline , relapse-related measures , MRI activity , and a st and ardized neuropsychological function test . Results : There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNβ-1b treatment groups . However , IFNβ-1b treatment result ed in improvement on secondary outcome measures involving clinical relapses , newly active MRI lesions , and accumulated burden of disease on T2-weighted MRI . Effects were similar for both IFNβ-1b treatment groups . Neutralizing antibodies to IFNβ-1b were detected in 23 % of 250-μg and 32 % of 160-μg/m2 recipients , but their presence did not consistently affect clinical or MRI outcomes . IFNβ-1b was also well tolerated at both doses . Conclusions : Although no treatment benefit was seen on the time to confirmed progression of disability , relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested , a result consistent with the outcomes of earlier clinical trials Background Interferon & bgr;-1a ( IFN&bgr;-1a , Avonex ) is efficacious in relapsing forms of MS . Studies of other IFN&bgr ; preparations in secondary progressive MS ( SPMS ) yielded conflicting results . This study was undertaken to determine whether IFN&bgr;-1a slowed disease progression in SP-MS . Methods A total of 436 subjects with SPMS and Exp and ed Disability Status Scale ( EDSS ) score 3.5 to 6.5 were r and omized to receive IFN&bgr;-1a  ( 60 & mgr;g ) or placebo by weekly intramuscular injection for 2 years . The primary outcome measure , used for the first time in a large-scale MS trial , was baseline to month 24 change in the MS Functional Composite ( MSFC ) , comprising quantitative tests of ambulation ( Timed 25-Foot Walk ) , arm function ( Nine-Hole Peg Test [ 9HPT ] ) , and cognition ( Paced Auditory Serial Addition Test [ PASAT ] ) . Results Median MSFC Z-score change was reduced 40.4 % in IFN&bgr;-1a subjects ( −0.096 vs −0.161 in placebo subjects , p = 0.033 ) , an effect driven mainly by the 9HPT and PASAT . There was no discernible benefit on the EDSS , which in this range principally reflects walking ability . IFN&bgr;-1a subjects had 33 % fewer relapses ( p = 0.008 ) . There was significant benefit on eight of 11 MS Quality of Life Inventory subscales . New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 ( both p < 0.001 ) . IFN&bgr;-1a was well tolerated by the majority of subjects . Neutralizing antibodies developed in 3.3 % of IFN&bgr;-1a – treated subjects . Conclusions IFN&bgr;-1a demonstrated benefit on MSFC progression , relapses , quality of life , and MRI activity in SPMS The accepted st and ard treatment of relapsing multiple sclerosis consists of medications for disease symptoms , including treatment for acute exacerbations . However , currently there is no therapy that alters the progression of physical disability associated with this disease . The purpose of this study was to determine whether interferon beta‐1a could slow the progressive , irreversible , neurological disability of relapsing multiple sclerosis . Three hundred one patients with relapsing multiple sclerosis were r and omized into a double‐blinded , placebo‐controlled , multicenter phase I11 trial of interferon beta‐la . Interferon beta‐la , 6.0 million units ( 30 μg ) , was administered by intramuscular injection weekly . The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Exp and ed Disability Status Scale ( EDSS )  . Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression ( p equals ; 0.02 ) . The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9 % in the placebo group and 21.9 % in the interferon beta‐la‐treated group . Patients treated with interferon beta‐la also had significantly fewer exacerbations ( p = 0.03 ) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images ( pvalues ranging between 0.02 and 0.05 ) . Over 2 years , the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients . There were no major adverse events related to treatment . Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients  by reducing the accumulation of permanent physical disability , exacerbation frequency , and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images . This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis There is currently no disease-modifying treatment proven to be of efficacy in primary progressive multiple sclerosis ( PPMS ) . However , a number of therapeutic trials have recently been specifically design ed for this group . These include a r and omised controlled trial of interferon beta-1a which is discussed here . It is hoped that therapeutics in primary progressive multiple sclerosis will continue to exp and and effective therapeutic agents will be developed The unique clinical characteristics of primary progressive multiple sclerosis ( PPMS ) pose particular diagnostic difficulties , both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS , which is not adequately addressed by current diagnostic criteria . This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS . ( We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made . ) Three levels of diagnostic certainty have been defined — definite , probable , and possible — based on clinical findings , abnormal cerebrospinal fluid , abnormalities on magnetic resonance imaging ( MRI ) of the brain and spinal cord , and evoked potentials . In definite PPMS , evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required : ( 1 ) nine brain lesions , ( 2 ) two spinal cord lesions , or ( 3 ) four to eight brain lesions and one spinal cord lesion . Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS : 64 % fulfilled the criteria for definite PPMS , 35 % for probable PPMS , and only 1 % for possible PPMS . These criteria now require prospect i ve validation in a cohort of newly diagnosed patients and by postmortem examination . Ann Neurol 
    Output:
    
Based on this review , the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients .
However , the trial population was too small to allow definitive conclusions on the efficacy of  ss-interferon  therapy in PPMS patients .