Cis Evolution Of The Influencing Factors Of Multiple Sclerosis Research And The Effect Of Interferon Intervention Meta Analysis

Objective To explore the influential factors for clinically isolated syndromes(CIS) evolving into clinical definite multiple sclerosis(CDMS),dangerous people for developing the disease will also be screened,which could be the basis for clinical preventive measures,thus to a larger degree decreasing disability out of CDMS. Methods This research adopted group sampling method and followed up regular visits to 123 CIS patients the hospitalized period from 2000 to 2007with the closing time being the time for CIS confirmed for transforming into CDMS.At the same time,the time for the first occurrence of the disease developing into CDMS was recorded with the closing time for regular visits being December,31,2007.In addition,by employing survival analysis for the follow-up visit data,the impacts resulting from different grouping upon survival rate and survival curves were compared. Apart from this,the relevant influential factors for CIS developing into CDMS were conducted statistical analysis,in which the data were carded on single-element Cox regressive analysis with SPSS13.0 software and then the screened influential factors were performed multi-element Cox regressive analysis.Results During the period of regular visits to patients there were 48 cases among the 123 CIS patients with CIS transforming into CDMS,amounting to 39%.After the Cox regressive analysis for the relevant influential factors,results can be reflected as follows:there existed some motivations before the occurrence of the disease with the relevant RR 2.60,95%confidential interval between 1.19 and 5.68(P=0.02 being the first time),the season for the first incidence of the disease was mostly summer with RR being 5.48,95%confidential interval between 1.84 and 16.3(P=0.002);hepatitis B surface antibody possessed RR 0.59,with 95%confidential interval between 0.33 and 1.04(P=0.07);finally there was statistic significance for CIS transforming into CDMS by employing intravenous immunoglobulin G for the first -time incidence of the disease with RR being 0.57 and 95%confidential interval between 0.31 and 1.07(P=0.08).Conclusions This study revealed some disadvantageous elements for the transformation,such as motivations before the occurrence of the disease;the season for the first-time incidence of the disease being summer;On the other hand,hepatitis B surface antibody showing positive and intravenous immunoglobulin G employed upon the first incidence of the disease may delay or prevent the occurrence of CDMS. Objective To evaluate the effectiveness and safety of using interferonβin contrast to placebo in treating subjects with CIS,RRMS and SPMS.Methods According to the evaluative methods of Cochrane Collaboration,the following data retrieval were conducted,including Cochrane Library(Central),MEDLINE,EMBase.Some Chinese neurological journals were also retrieved manually.In addition,randomized contrast trials(RCTs) by adopting interferon-beta and placebo for CIS,RRMS and SPMS were collected and the quality of methodology in those trials was critically assessed.Finally,the Cochrane Collaboration's RevMan 4.2.10 software was employed for data analysis.Results The following results in this research were demonstrated.(1) Four RCTs with interferon-beta in contrast to placebo for CIS were included,involving 1362 patients.All included studies were graded in term of randomization,allocation and blinding with one study for A level and the other three for B level.Meta-analysis shows that the occurrence of CIS to CDMS by interferon-beta was lower than that by placebo[RR0.64,95%CI(0.55,0.73), p＜0.0001]with NNT 6.Besides,the size of MRI T₂ lesions,the number of new T₂ lesions or of enlarged lesions and Gd-enhancing lesions in interferon-beta group were significantly decreased, compared with those in placebo group.On the other hand,some adverse reactions were found with more frequent occurrence in interferon-beta group than those in placebo group,which can be indicated as follows:flu-like syndromes[RR1.88,95%CI(1.03,3.42),p=0.04],injection site reaction[RR5.28,95%CI(3.85,7.23),p=＜0.001],fever[RR2.55,95%CI(1.52,4.26),p=0.0004], myalgia[RR1.87,95%CI(1.03,3.42),p=0.04],leukopenia[RR3.19,95%CI(1.67,6.12), p=0.0005],enhancing of aminotransferase[RR4.69,95%CI(2.40,9.15),p＜0.0001].Moreover, as for depression[RR1.22,95%CI(0.86,1.73),p=0.26]and chills[RR1.51,95%CI(0.63,3.59), p=0.35]there was no significance between two groups.(2) Four RCTs were involved which compared the treating results by using interferon-beta and placebo for RRMS with 1117 patients. This time again the relevant studies were graded in term of randomization,allocation and blinding with three studies for A level and one for B level.Meta-analysis reflects that the following items through interferon-beta treatment decreased compared with those in placebo group,including relapse rate[RR0.82,95%CI(0.75,0.90),p＜0.001]and sustained progression in disability from RRMS transformation[RR0.70,95%CI(0.56,0.89),p=0.001],and also reduced MRI lesions including T₂ lesion volume,new lesions or enlarged lesions and Gd enhancing lesions.Apart from these,there were less participants who needed steroid treatment than those for placebo[RR0.70,95%CI(0.56,0.87),p=0.001].In terms of reports of side effects from clinics and laboratory,the occurrence of some syndromes in interferon-beta had higher frequency than that in placebo group,which can be demonstrated as follows:flu-like syndromes[RR1.70,95%CI(1.23,2.37),p=0.001],fever[RR1.92,95%CI(1.52,2.42),p＜0.0001], myalgia[RR1.88,95%CI(1.47,2.40),p=0.04],chill[RR2.32,95%CI(1.39,3.88),p=0.001], leukopenia[RR4.51,95%CI(2.14,9.51),p=0.001],enhancing of aminotransferase[RR3.62,95% CI(1.83,7.18),p=0.0002].However,there was no significance between the two group among the following items:nausea and diarrhea[RR1.51,95%CI(0.94,2.03),p=0.10],depression [RR0.96,95%CI(0.74,1.24),p=0.74],asthenia[RR1.27,95%CI(0.92,1.76),p=0.15],reaction in injection-site[RR2.40,95%CI(0.94,6.13),p=0.07],and headache[RR1.19,95%CI(1.04,1.36), p=0.15].(3) Five RCTs comparing interferon-beta versus placebo for SPMS involving 2552 patients were included.The studies were graded in term of randomization,allocation and blinding with two studies for A level and three for B level.Meta-analysis reveals that the occurrence of exacerbation[RR0.84,95%CI(0.76,0.92),p=0.003]and progression of the disease [RR0.86,95%CI(0.76,0.98),p=0.02]by interferon beta had been lowered compared with those in placebo group.Moreover,the number of patients who underwent steroid administration was significantly reduced[RR0.79,95%CI(0.70,0.89),p=0.0001]in the interferon beta group with interferon beta resulting in a reduction of the size of MRI T₂ lesion,new lesion or enlarged lesion and Gd enhancing lesion.As to the patients who needed hospitalization,there was no significance between the two groups.Based on the reports of side effects from clinics and laboratory,some adverse events resulting from interferon beta possessed higher frequency than those from placebo,which included:injection-site reaction[RR3.07,95%CI(1.77,5.31), p＜0.0001],injection-site infection[RR0.64,95%CI(6.99,16.19),p＜0.0001],injection-site necrosis[RR35.99,95%CI(4.95,261.50),p=0.0004],fever[RR2.91,95%CI(2.20,3.85),p＜0.0001], depression[RR1.24,95%CI(1.02.1.51),p=0.03],hypertension[RR3.64,95%CI(1.35,16.01), p=0.02],leukopenia[RR2.87,95%CI(1.34,6.14),p=0.007],lymphopenia[RR1.35,95%CI (1.10,1.66),p=0.0006],headache[RR2.22,95%CI(1.38,3.57),p=0.0009],enhancing of aspartate aminotransferase[RR4.52,95%CI(1.91,10.72),p=0.0006].On the other hand, concerning flu-like syndromes[RR1.36,95%CI(0,93,1.98),p=0.11],chills[RR3.02, 95%CI(1.99,4.59),p=0.05],asthenia[RR1.46,95%CI(0.90,2.36),p=0.13]and enhancing of alanine aminotransferase[RR1.87,95%CI(0.61,5.87),p=0.27],there was no significance between the two groups.Conclusions(1) The occurrence from CIS to CDMS by using interferon beta treatment was lowered.(2) By means of interferon beta treatment,the relapse rate and sustained progression in disability from RRMS transformation were decreased.(3) Through interferon beta treatment the occurrence of exacerbation from SPMS and the occurrence of progression of the disease were reduced.(4) Interferon beta treatment could result in a significant reduction of the size of MRI T₂ lesion,new lesion or enlarged lesion and Gd enhancing lesion.(5) Both clinical and laboratory side effects were more frequent in interferon beta group than those in placebo group,which involved:flu-like syndrome,fever,myalgia,chills,leukopenia,lymphopenia,enhancing of aminotransferase,injection-site reaction,injection-site infection and injection-site necrosis.