***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 
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    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 Our previously reported multicenter , blinded , r and omized , controlled study of two doses of interferon beta-1b ( IFNB ) in 372 patients demonstrated a reduction in relapse frequency and severity and in MRI activity . We now report the results of the continuation of that study . The median time on study was 46.0 months for the placebo arm , 45.0 months for 1.6 million international units ( MIU ) , and 48.0 months for 8 MIU . IFNB had a persistent beneficial effect on exacerbation rate and MRI burden of disease and was relatively free of long-term side effects . There was a one-third reduction in exacerbation rate in the 8-MIU treatment arm , compared with placebo , in each of 5 years . Serial annual MRI was done in all patients , and 217 of the patients had either a fourth- or fifth-year scan . There was no significant progression of lesion burden in the 8-MIU arm in each successive year compared with baseline ( at 4 years , p = 0.917 ) , whereas a highly significant increase in lesion area occurred in the placebo arm ( p = 0.0001 ) . Among the 154 noncompleters , there was no systematic bias recognized that favored either treatment arm for the outcome measures of exacerbation rate , disability , or MRI activity . Dropouts in the placebo group had higher exacerbation rates and accumulation of MRI lesion burden than did dropouts in the other treatment arms , which probably reduced the power of the study to demonstrate treatment effects on these measures in the later years of the trial . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To investigate whether ingested human recombinant interferon-alpha2a ( IFN-alpha2a ) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS ( RRMS ) . METHODS Entry criteria included clinical ly definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI . RESULTS Of 80 patients screened , 33 were eligible and 30 patients were enrolled for treatment . Patients were r and omized ( 10 per group ) to placebo , 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months . They were examined clinical ly and with monthly cerebral MRI . Sample size projections were based on the assumption of a parenteral IFN-like effect , a 90 % reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable . RESULTS There was no significant effect on enhancing lesions . However , post hoc analysis suggested a possible treatment effect in the 10,000 IU group . By direct monthly comparison of placebo and 10,000 IU group in treatment month 5 , there were 73 % ( p < 0.05 ) fewer enhancements in the 10,000 IU group than in the placebo group . There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5 . Relapses and adverse events were not different among the treatment groups . Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies . CONCLUSIONS This trial showed no benefit based on the primary outcome measure . Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect , IFN-alpha may deserve further study OBJECTIVE To compare efficacy of interferon beta-1a , 22 microg or 44 microg weekly , with placebo in relapsing MS . BACKGROUND Uncertainty exists concerning the optimal dose regimen for interferon beta in relapsing-remitting MS . Many patients and physicians prefer the convenience and lesser side effects of an injection given once weekly ( qw ) as opposed to three times weekly . Pharmacokinetic data and information on biologic markers suggest that this frequency may be suboptimal . METHODS R and omized , double-blind study of interferon beta-1a 22 microg , 44 microg , or placebo administered by weekly subcutaneous injection for 48 weeks . Proton density (PD)/T2-weighted and T1-weighted-gadolinium MRI scans during 24 weeks of therapy were analyzed for the number of combined unique ( CU ) lesions ( primary outcome ) . Biannual PD/T2 scans were analyzed for T2 activity and burden of disease ( BOD ) . RESULTS CU lesions at 24 weeks had a median of 0.71/scan with placebo , 0.5/scan with 22 microg ( not significant ) , and 0.33/scan with 44 microg ( p = 0.002 ) . T2 new lesion count/scan ( mean/median ) at 48 weeks was 3.2/1.5 for placebo , 2.4/1.0 for 22 microg ( p = 0.03 ) , and 1.5/1.0 for 44 microg ( p = 0.0005 ) . BOD at 48 weeks showed a median increase of 5.9 % for placebo compared with a decrease of 1.4 % in the 44 microg group ( p = 0.0058 ) and 2 % in the 22 microg group ( p = 0.0018 ) . No clinical variable , apart from steroid use in the 44 microg qw group ( p = 0.014 ) , showed significance . CONCLUSIONS These data confirm an MRI benefit of interferon beta-1a at low dose in MS , but highlight the limited clinical effect . Taken together with other studies , the data demonstrate a dose-effect relationship for both clinical and MRI variables 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 Abstract Objective : To evaluate the cost utility of interferon beta-1b in secondary progressive multiple sclerosis . Design : Population based cost utility model ( healthcare perspective ) . Data on use of health services were obtained from case records and routine morbidity data and utility values from a EuroQol survey . Local and published costs were used . Effectiveness was modelled using data on relative risk reductions from a r and omised trial of interferon beta-1b . Setting : Tayside region , 1993 - 5 . Subjects : 132 ambulatory people with secondary progressive multiple sclerosis . Main outcome measures : Cost per quality adjusted life year ( QALY ) gained . Rate of relapse and proportion becoming wheelchair dependent over three years . Results : The number needed to treat for 30 months to delay time to wheelchair dependence in one person by nine months was 18 ( 95 % confidence interval 5 to 26 ) . For every 18 people treated for 30 months , six relapses would be prevented , gaining 0.397 discounted QALYs . The cost per QALY gained was £ 1 024 667 ( £ 276 466 to £ 1 485 499 ) . If treatment was restricted to patients attending neurology services , the number needed to treat was 14 ( cost per QALY gained £ 833 514 ( £ 161 358 to ∞ ) ) . The cost per QALY gained was not sensitive to changes in cost which took account of a societal perspective . Conclusions : The cost per QALY gained from interferon beta is high because of the high drug cost and modest clinical effect . Re sources could be used more efficiently elsewhere . Key messages Secondary progressive multiple sclerosis is a potentially disabling disorder associated with low health related quality of life Interferon beta-1b may reduce rate of relapse The benefits of interferon beta-1b treatment are very low relative to its cost Cost utility analysis estimated a cost of over £ 1 m per QALY gained Cost per QALY was not affected by taking into account the costs of care Money would be better spent on other ways of improving quality of life than on interferon The role of interferon-alpha ( IFN-alpha ) and transfer factor ( TF ) in the treatment of multiple sclerosis was investigated in a prospect i ve , multi-centric , three year , double-blind , placebo-controlled trial . One hundred and eighty two patients with clinical ly definite multiple sclerosis were r and omised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status . Subcutaneous injections of IFN-alpha ( 3 x 10(6 ) units ) , TF ( 0.5 units ) manufactured from leucocytes of cohabiting donors , or placebo were given twice weekly for two months , once weekly for 10 months then fortnightly for 24 months . One hundred and fifty three patients completed the injection regimen . There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group . Similarly , change in visual evoked responses ( VER ) , and in number of oligoclonal b and s ( OCB ) and the level of myelin basic protein ( MBP ) in the cerebrospinal fluid ( CSF ) over the trial period did not differ significantly between the three groups . However , the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups Ten patients with multiple sclerosis who were treated with human fibroblast interferon ( IFN-B ) for 6 months showed a significant reduction in their exacerbation rates compared with their rates before treatment ( P < .01 ) . The IFN-B was administered intrathecally by serial lumbar punctures . There was no significant change in the exacerbation rates of ten multiple sclerosis control patients before and during the period of observation . The  IFN-B recipients have now been on the study a mean of 1.5 years , the controls , 1.2 years . The clinical condition of five of the IFN-B recipients and one of the control patients has improved , whereas the condition of five of the controls and one of the IFN-B recipients has deteriorated ( P < .036 ) . These findings warrant cautious optimism about the efficacy of intrathecal IFN-B in altering the course of multiple sclerosis and support concepts of a viral or dysimmune etiology of the disease Sixteen patients with clinical ly definite MS admitted to a double blind r and omised controlled trial of intrathecal natural beta-IFN were followed for a mean of 22 months including the six month treatment period . Clinical response , evaluated in terms of relapse frequency and of progression rate , showed an increase in relapse rate in treated patients during the six month treatment period and , overall , no benefit in treated versus placebo patients . Serial evaluations were made of cerebrospinal fluid ( CSF ) cells , IgG , myelin basic protein and CSF and blood T-cell subsets . A rise in CSF IgG Index , MBP and DR+ cells in IFN-treated patients suggested an activation of intrathecal immune response in treated patients BACKGROUND A recombinant form of interferon beta-1b ( Betaseron ) was given Food and Drug Administration approval for use in the treatment of relapsing-remitting multiple sclerosis in 1993 based on a documented reduction in exacerbation rate . However , its effect on disease progression is less clear . It costs $ 11,000 per year and has documented adverse effects such as fatigue , feverlike symptoms , and depression . OBJECTIVES To evaluate a recombinant form of interferon beta-1b in the treatment of relapsing-remitting multiple sclerosis and to discuss treatment trade-offs and comprehensive quality -of-life ( QOL ) outcomes . METHODS We present a r and omized evaluation of treatment with a recombinant 
    Output:
    
Side-effects were common , and acute toxic effects adversely affected quality of life .
INTERPRETATION Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment .