Efficacy And Safety Of Intravenous Immunoglobulin In Multiple Sclerosis: A Meta-analysis

Objective To evaluate the effectiveness and safety of intravenous immunoglobulin in patients with multiple sclerosis.Methods We searched The Cochrane Library(Issue 4,2010), MEDLINE ( 1950 to October 2010), EMbase (1966 to October 2010), CBM(1978 to October 2010), CNKI(1979 to October 2010), VIP(1989 to October 2010)and Wan fang(1999 to October 2010), we also scanned references of all included studies and pertinent reviews. The quality of included studies was critically assessed. We used the RevMan 5.0.2 software provided by Cochrane Collaboration for data analysis.Result A total of 934 articles were retrieved, but only 15 randomized controlled trials were finally included, involving 1394 patients. 1) Two RCTs with intravenous immunoglobulin for clinically isolated syndrome (CIS) were included, involving 159 patients. All included studies were graded, two RCTs are A level. Meta-analysis showed: The relapse rate in patients receiving IVIG [RR=0.56, 95%CI (0.30, 1.02), P=0.06], There were no significant differences between IVIG group and placebo group. 2) Seven RCTs with intravenous immunoglobulin for Relapsing-Remitting multiple sclerosis were included, involving 480 patients. All included studies were graded, two RCTs are A level, two RCTs are B level and the others for C level. Meta-analysis showed:â‘ the rate of sustained progression in disability in patients receiving IVIG [RR=0.72, 95%CI (0.56, 0.93), P=0.01]. There were significant differences between IVIG group and placebo group.â‘¡the relapse rate in patients receiving IVIG [R =0.75, 95%CI (0.61, 0.94), P=0.01], There were significant differences between IVIG group and placebo group.â‘¢The change of EDSS scored in patients receiving IVIG [WMD=-0.35, 95%CI(-0.47, -0.23), P<0.00001].There were significant differences between IVIG group and placebo group. 3) Three RCTs with intravenous immunoglobulin for Secondary-progressive multiple sclerosis were included, involving 549 patients. The graded of three RCTs is B level. Meta-analysis showed: The rate of sustained progression in disability in patients receiving IVIG[RR=0.98,95%CI(0.84,1.13),P=0.75]; The relapse rate in patients receiving IVIG [RR=1.07, 95%CI(0.88, 1.29), P= 0.50], There were no significant differences between IVIG group and placebo group.4) Safety of intravenous immunoglobulin: Rate of occurrence of adverse events was reported in twelve RCTs, Meta-analysis showed: Headaches[RR=1.60, 95%CI(1.13,2.27), P=0.008]; Nausea [RR =2.03, 95%CI(0.85, 4.84), P=0.11];Rash[RR =3.27, 95%CI(1.82, 5.86), P<0.0001];[RR=3.00, 95% CI (0.32, 28.01), P=0.34]; Pulmonary embolism [RR=2.60, 95% CI (0.61, 11.11), P =0.20].Conclusions 1) IVIG tends to have better efficacy and safety compared with placebo.2) By means of IVIG treatment, the relapse rate and sustained progression in disability from RRMS transformation were decreased. The EDSS scored were cut down by IVIG. 3) By means of IVIG treatment, the relapse rate and sustained progression in disability from SPMS transformation were not decreased.4) Headaches and rash were frequent seen in IVIG. Compared with placebo, pulmonary embolism and depression has no significant differences between IVIG group and placebo group. More well-designed Multi-center large-scale randomized controlled trials are needed to confirm this.