***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: Pulse methylprednisolone therapy has dramatic effects on clinical and immunological parameters of disease activity in patients with rheumatoid arthritis . Previous studies of this treatment have all used the intravenous route and methylprednisolone succinate . This study addresses the question of whether oral prednisolone in equivalent doses can substitute for intravenous methylprednisolone in pulse therapy in a double blind parallel study . It is shown that oral prednisolone has clinical and immunological effects equivalent to those of intravenous methylprednisolone , making it possible to administer pulse therapy to patients with rheumatoid arthritis as out patients without the inconvenience and inherent dangers of intravenous administration This was a single-blind , single-dose , r and omized crossover study to determine the absolute bioavailability of Medrol , a new high dose ( 100 mg ) methylprednisolone tablet product , by comparing it with 100 mg methylprednisolone from an intravenous formulation , Solu-Medrol .  Fourteen healthy , non-smoking , Caucasian male volunteers took part . On treatment days volunteers remained recumbent for 4 hours after drug administration , with food and fluid intake st and ardized over this period . Serial blood sample s were drawn over a 14-hour period after drug administration . Plasma methylprednisolone concentrations were determined by high performance liquid chromatography . The geometric means of AUCi.v . and AUCtablet were 4,049 and 3,334 ng.h/ml , respectively . The absolute bioavailability of the tablet product was 82 % , which is in agreement with published data for other oral dosage forms of methylprednisolone . Volunteers displayed the expected rise in peripheral blood neutrophil count , but no other clinical ly relevant changes in hematology or clinical chemistry were observed . No adverse drug reactions were recorded . It is concluded that the tablet product can be used as a substitute for parenteral methylprednisolone in situations requiring high-dose therapy BACKGROUND High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis , but can be inconvenient and expensive . We aim ed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration . METHODS We did this multicentre , double-blind , r and omised , controlled , non-inferiority trial at 13 centres for multiple sclerosis in France . We enrolled patients aged 18 - 55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale .  With use of a computer-generated r and omisation list and in blocks of four , we r and omly assigned ( 1:1 ) patients to either oral or intravenous methylprednisolone , 1000 mg , once a day for 3 days . Patients , treating physicians and nurses , and data and outcome assessors were all masked to treatment allocation , which was achieved with the use of saline solution and placebo capsules . The primary endpoint was the proportion of patients who had improved by day 28 ( decrease of at least one point in most affected score on Kurtzke Functional System Scale ) , without need for retreatment with corticosteroids , in the per- protocol population . The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15 % . This trial is registered with Clinical Trials.gov , number NCT00984984 . FINDINGS Between Jan 29 , 2008 , and June 14 , 2013 , we screened 200 patients and enrolled 199 . We r and omly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days ( SD 3·6 ) and 7·4 days ( 3·9 ) , respectively . In the per- protocol population , 66 ( 81 % ) of 82 patients in the oral group and 72 ( 80 % ) of 90 patients in the intravenous group achieved the primary endpoint ( absolute treatment difference 0·5 % , 90 % CI -9·5 to 10·4 ) . Rates of adverse events were similar , but insomnia was more frequently reported in the oral group ( 77 [ 77 % ] ) than in the intravenous group ( 63 [ 64 % ] ) . INTERPRETATION Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile . This finding could have implication s for access to treatment , patient comfort , and cost , but indication should always be properly considered by clinicians . FUNDING French Health Ministry , Ligue Française contre la SEP , Teva Relapses of multiple sclerosis ( MS ) are treated commonly with high‐dose intravenous methylprednisolone ( MP ) given over a period of 3–5 days . The mechanisms responsible for the beneficial effects of MP in attacks are not clearly established . It is also controversial whether this treatment may have a long‐term effect . Here , peripheral blood sample s from relapsing – remitting MS patients in acute relapse were analysed by flow cytometry just before steroid treatment and at different time points after initiation of the therapy . We observed an immediate ( day 3 ) decrease in the percentage of CD4 + lymphocytes , with a relative increase in the memory ( CD4+CD45R0 + ) sub population . A longer st and ing effect of MP on IFN‐γ production , CD54 , CCR5 , CXCR3 and CD95 ( Fas ) expression was also observed on CD4 + cells after 1 month of treatment initiation . Six months after the therapy , during clinical remission , no changes due to ivMP therapy were detected . These results support that MP treatment of relapses induces immediate post‐treatment and short‐term effects on the immune system that could partly account for the clinical and radiological improvement observed in MS patients . However , no conclussion can be drawn as to a possible long‐term or even intermediate influence of ivMP treatment on the course of the disease We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis . Following a double blind trial design ed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis , 80 patients were followed for two years with six-monthly assessment s during which all subsequent relapses were recorded . The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients ( 1.06 vs. 0.78 ) , but the adjusted difference between the two groups was not statistically significant ( 0.18 ; 95 % CI -0.19 to 0.55 , P=0.3 ) . The time to onset and the severity of the first relapse after treatment , the number of relapse free patients at the end of the follow-up period , and the severity of the relapses during the follow-up period were similar in the two groups . This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment Background : IV methylprednisolone ( IVMP ) has been used to treat relapses in patients with relapsing-remitting ( RR ) MS , but its effect on disease progression is not known . Furthermore , there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy . Objective : To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS . Methods : The authors conducted a r and omized , controlled , single-blind , phase II clinical trial of IVMP in patients with RR-MS . Eighty-eight patients with RR-MS with baseline Exp and ed Disability Status Scale ( EDSS ) scores of ≤5.5 were r and omly assigned to regular pulses of IVMP ( 1 g/day for 5 days with an oral prednisone taper ) or IVMP at the same dose schedule only for relapses ( IVMP for relapses ) and followed without other disease-modifying drug therapy for 5 years . Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years . Patients had quantitative cranial MRI scans at study entry and after 5 years and st and ardized clinical assessment s every 4 to 6 months . Results : Eighty-one of 88 patients completed the trial as planned , and treatment was well tolerated . Baseline demographic , clinical , and MRI measures were well matched in the two study arms . Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study ( p < 0.0001 ) . Mean change in T1 black hole volume  favored pulsed IVMP therapy ( + 1.3 vs + 5.2 mL ; p < 0.0001 ) , as did mean change in brain parenchymal volume ( + 2.6 vs −74.5 mL ; p = 0.003 ) . There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study . However , there was significantly more EDSS score worsening in the control group , receiving IVMP only for relapses . There was a 32.2 % reduction ( p ≤ 0.0001 ) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm . At the end of the study , EDSS was better in the pulsed MP group ( 1.7 vs 3.4 ; p < 0.0001 ) . Prolonged treatment with pulsed IVMP was safe and well tolerated ; only two patients dropped out for toxic side effects over 5 years . Conclusions : In patients with RR-MS , treatment with pulses of IVMP slows development of T1 black holes , prevents or delays whole-brain atrophy , and prevents or delays disability progression . A phase III study of IVMP pulses is warranted Background : Steroids improve multiple sclerosis ( MS ) relapses but therapeutic window and dose , frequency and administration route remain uncertain . Objective : The objective of this paper is to compare the clinical and radiologic efficacy , tolerability and safety of intravenous methylprednisolone ( ivMP ) vs oral methylprednisolone ( oMP ) , at equivalent high doses , for MS relapse . Methods : Forty-nine patients with moderate or severe relapse within the previous 15 days were r and omized in a double-blind , noninferiority , multicenter trial to receive ivMP or oMP and their matching placebos .  Exp and ed Disability Status Scale ( EDSS ) scores were determined at baseline and weeks 1 , 4 and 12 . Brain MRI were assessed at baseline and at weeks 1 and 4 . Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks ( noninferiority margin of one point ) , with further key efficacy assessment s of number and volume of T1 gadolinium-enhancing ( Gd+ ) , and new or enlarged T2 lesions at four weeks ’ post-treatment initiation . Secondary outcomes were safety and tolerability . Results : The study achieved the main outcome of noninferiority at four weeks for improved EDSS score . No differences were found between ivMP and oMP in the number of Gd+ lesions ( 0 ( 0–1 ) vs 0 ( 0–0.5 ) , p = 0.630 ) , volume of Gd+ lesions ( 0 ( 0–88.0 ) vs 0 ( 0–32.9 ) mm3 , p = 0.735 ) , or new or enlarged T2 lesions ( 0 ( 0–194 ) vs 0 ( 0–123 ) , p = 0.769 ) . MP was well tolerated , and no serious adverse events were reported . Conclusions : This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS , similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe . Trial registration : clinical trials.gov identifier : Oral prednisone 1might be a convenient , inexpensive alternative to IV methylprednisolone ( IVMP ) if the bioequivalent dose was known . We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis ( MS ) . At 24 hours , the mean area under the concentration-time curve ( AUC ) , the main component of bioavailability , did not differ between groups ( p = 0.122 ) . This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses Our aim was to investigate differences in immune mechanisms in multiple sclerosis ( MS ) relapse , after high-dose oral methylprednisolone ( oMP ) or intravenous methylprednisolone ( ivMP ) . We measured serum cytokines ( IL-2 , IL-4 , IL-6 , IL-10 , IL-17 , TNF-α and IFN-γ ) in 39 of 49 MS patients with moderate-severe relapse , whom were treated with ivMP or oMP  in a placebo-controlled , non-inferiority clinical trial . We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment . The cytokine 
    Output:
    
In adult patients with acute MS relapse , there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids