***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 Fifty-eight patients with severe , progressive multiple sclerosis were prospect ively r and omized to one of three treatments : 20 received intravenous ACTH , 20 received high-dose intravenous cyclophosphamide plus ACTH , and 18 were placed on a regimen consisting of plasma exchange , low-dose oral cyclophosphamide , and ACTH . The three groups were similar in age , sex , duration and type of disease , and degree of disability . Before treatment and six months and one year after treatment , a disability-status score , ambulation index , and functional-status score were determined , and a quantitative neurologic examination was performed . In the ACTH group , the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year ; in the cyclophosphamide-ACTH group , 18 of 20 at six months and 16 of 20 at one year ; and in the plasma exchange group , 11 of 18 at six months and 9 of 18 at one year . High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months ( at 12 months , cyclophosphamide-ACTH vs. ACTH , P = 0.0004 ; cyclophosphamide-ACTH vs. plasma exchange , P = 0.087 ) . Thus , progressive multiple sclerosis may be stabilized by short-term , intensive immunosuppression with cyclophosphamide plus ACTH Background and Objective : A phase III double-blind , placebo-controlled clinical trial demonstrated that interferon beta-la ( IFNβ-1a ) ( Avonex , Biogen ) significantly delayed progression of disability in relapsing MS patients . The primary clinical outcome was time from study entry until disability progression , defined as≥1.0 point worsening from baseline Kurtzke Exp and ed Disability Status Scale ( EDSS ) score persisting for at least two consecutive scheduled visits separated by 6 months . The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance . Methods : Post hoc analyses related to disability outcomes using data collected during the double-blind , placebo-controlled phase III clinical trial . Results : ( 1 ) Clinical efficacy related to disability did not depend on the definition of disability progression . A significant benefit in favor of IFNβ-1a was observed when ≥2.0 point worsening from baseline EDSS was required or when worsening was required to persist for ≥1.0 year . ( 2 )  Placebo recipients who reached the primary clinical outcome worsened by a larger amount from baseline EDSS than did  IFNβ-1a recipients who reached the primary study outcome . ( 3 ) Significantly fewer IFNβ-1a recipients progressed to EDSS milestones of 4.0 ( relatively severe impairment ) or 6.0(unilateral assistance needed to walk ) . ( 4 ) Cox proportional hazards models demonstrated that the only baseline characteristic strongly correlated with longer time to disability progression  was IFNβ-1a treatment . Conclusions : The primary clinical outcome for the IFNβ-1a clinical trial underestimated clinical benefits of treatment . Results in this report demonstrate that IFNβ-1a treatment is associated with robust , clinical ly important beneficial effects on disability progression in relapsing MS patients BACKGROUND The Multiple Sclerosis Functional Composite ( MSFC ) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation ( Timed 25-Foot Walk ) , arm function ( 9-Hole Peg Test ) , and cognitive function ( Paced Auditory Serial Addition Test ) . The MSFC is the primary outcome measure in the ongoing multinational phase 3 trial of interferon beta-1a ( Avonex ) in patients with secondary progressive MS . OBJECTIVE To assess the practice effects , reliability , and validity of the MSFC clinical outcome measure . DESIGN Examining technicians underwent formal training using st and ardized material s. The MSFC was performed according to a st and ardized protocol . The 436 patients enrolled in the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial underwent 3 prebaseline MSFC testing sessions before r and omization . RESULTS Practice effects were evident initially for the MSFC but stabilized by the fourth administration . The Paced Auditory Serial Addition Test demonstrated the most prominent practice effects . The reliability of the MSFC was excellent , with an intraclass correlation coefficient for session 3 ( final prebaseline session ) vs session 4 ( baseline ) of 0.90 . The MSFC at baseline correlated moderately strongly with the Kurtzke Exp and ed Disability Status Scale . Among the MSFC components , the Timed 25-Foot Walk correlated most closely . Correlations among the 3 MSFC components were weak , suggesting they assess distinct aspects of neurologic function in patients with MS . CONCLUSIONS The MSFC demonstrated excellent intrarater reliability in this multinational phase 3 trial . Three prebaseline testing sessions were sufficient to compensate for practice effects . The pattern of correlations among the MSFC , its components , and the Kurtzke Exp and ed Disability Status Scale supported the validity of the MSFC BACKGROUND Although the risk of clinical attacks of multiple sclerosis seems to be significantly increased with viral upper respiratory tract infections ( URTI ) , serological evidence for the reported association remains controversial . In addition , although MRI is six to 10 times more sensitive than clinical exacerbations in indexing disease activity , any possible association between URTI and MRI activity has yet to be investigated . OBJECTIVES To examine the relation between URTI and disease activity , in multiple sclerosis patients participating in a placebo controlled trial of interferon β-1a  , as indexed both by clinical exacerbation rate and by the number and volume of gadolinium - diethylenetriaminepenta acetic acid ( Gd-DTPA ) enhancing lesions on MRI  . “ At risk ” periods were defined around symptomatic URTI , with or without serological confirmation . RESULTS The relative risk of clinical relapse for serologically unconfirmed symptomatic URTI was 2.1 ( p=0.004 ) . Raised antiviral antibody titres conferred a relative risk of multiple sclerosis exacerbations that was 3.4 times higher than the “ not at risk ” periods ( annual attack rates of 5.7 v 1.6 , respectively , p=0.006 ) . There was no definite relation between the number or the volume of active lesions on MRI and either symptomatic or serologically defined at risk periods . CONCLUSIONS These results confirm the previously reported association between viral infections and multiple sclerosis exacerbations and indicate that the relative risk may be even higher when viral infection is serologically confirmed . However , the results , perhaps because of the confounding effects of interferon β-1a , do not provide convincing evidence of increased blood-brain barrier breakdown or inflammation during periods of virally induced immune stimulation OBJECTIVE : To evaluate whether recombinant human interferon-beta-1a significantly affects disease activity as measured by a reduction in the number and volume of Gd enhancing lesions on monthly MRI . The study also evaluated the effect on six-monthly T2 weighted abnormality and relapse frequency . METHODS : After a baseline scan and a six month pretreatment period , 68 patients were r and omly assigned to receive either 3 MIU or 9 MIU of interferon-beta-1a by subcutaneous injection three times a week for six months . All patients were examined by Gd enhanced MRI every month in both pretreatment and treatment periods . The evaluation of Gd enhancing lesions was performed blind at the end of the study . RESULTS : The mean number of Gd enhancing lesions was higher during the pretreatment period than during treatment . This difference was statistically significant for the two different dose subgroups ( 3.5 v 1.8 , P < 0.001 for the 3 MIU group and 2.4 v 0.9 , P < 0.001 for the 9 MIU group , corresponding to a reduction of 49 % and 64 % respectively ) . The mean volume of Gd enhancing lesions also significantly decreased by 61 % ( 3 MIU group ) and 73 % ( 9 MIU group ) . These reductions were evident only after the first month of treatment . The six-monthly rate of new lesions as seen in T2 weighted images showed a similar trend of reduction with treatment ( 65 % and 70 % respectively ) . Lesion volume on T2 scans significantly increased during the pretreatment period whereas it remained almost stable during the treatment period in both groups . Clinical relapse rate was significantly reduced by treatment ( 53 % for the 3 MIU group , P < 0.001 ; 69 % for the 9 MIU group , P < 0.001 ) . CONCLUSION : Interferon-beta-1a seemed effective in reducing disease activity in relapsing-remitting multiple sclerosis at both the doses used A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b ( Betaseron , Berlex Laboratories , Richmond , CA ) , in patients with relapsing-remitting multiple sclerosis ( RRMS ) . During the initial dose finding period ( 24 weeks ) , five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8 , 4 , 8 , or 16 million units ( mU ) of Betaseron or placebo ( WHO St and ard ) . Although some side effects were noted in all groups , a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted . Patients given 16 mU had no exacerbations during the initial dosing period , but associated side effects led to dose reduction or dropout . An 8 mU dose was selected for further study after 24 weeks , and continuous dosing at 8 mU in 15 patients has now exceeded 6 years . Side effects abated over time . Neutralizing antibody developed in most patients , but titers were variable , fluctuated independently of clinical course , and tended to fall with prolonged treatment . A dose-dependent rise in neopterin levels was observed during the initial dosing period . This pilot study has demonstrated responsiveness to Betaseron , shown a stable safety profile over time , and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS The immunological effects of long-term treatment with recombinant alpha-2 interferon ( rIFN-alpha 2 ) were investigated in multiple sclerosis ( MS ) patients treated with 2 X 10(6 ) units of IFN or a placebo three times per week for one year . A mild lymphopenia was observed in IFN patients who also showed a decrease in the absolute number of total T cells in the blood ( OKT3 binding cells ) ; however , the percentage of cells reacting with OKT3 , OKT4 , and OKT8 antibodies did not change significantly during the study . The percentage of cells reacting with the Leu-7 antibody , which recognizes NK cells , was unchanged . During MS exacerbations , placebo patients showed a tendency for decreased levels of OKT3 and OKT8 cells . In contrast , IFN patients did not demonstrate a decrease in either OKT3 or OKT8 cells during disease attacks . Concanavalin A (ConA)-induced suppressor cell activity was depressed in both IFN and placebo-treated patients during attacks . Lymphoproliferative responses to phytohemagglutinin , pokeweed mitogen , and ConA were unchanged . These studies demonstrate that long-term treatment with rIFN-alpha 2 induces a generalized T-cell lymphopenia , but at this dose does not significantly affect the profiles of T-cell subsets and suppressor cell function in MS patients Background : Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later , presumably due to myelin and axonal injury . MRI demonstrates ongoing disease activity during the early disease stage , even in some patients who are stable clinical ly . The optimal MRI measure for the destructive pathologic process is uncertain , however . Methods : In this post-hoc study ,  MRI scans were analyzed from patients with relapsing MS participating in a placebo-controlled trial of interferon β-1a .  The brain parenchymal fraction , defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour , was used to measure whole brain atrophy . The relationship between disease features and brain atrophy and effect of interferon β-1a were determined . Results : MS patients  had significant brain atrophy that worsened during each of 2 years of observation . In many patients , brain atrophy worsened without clinical disease activity . Baseline clinical and MRI abnormalities were not strongly related to the rate of brain atrophy during the subsequent 2 years . Treatment with interferon β-1a result ed in a reduction in brain atrophy progression during the second year of the clinical trial . Conclusions : Patients with relapsing 
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However , the correct assignment of dropouts was essential to the demonstration of efficacy , most conspicuously concerning the effect of the drug on disease progression .
REVIEW ER 'S CONCLUSIONS The efficacy of interferon on exacerbations and disease progression in patients with relapsing remitting MS was modest after one and two years of treatment .