A Systematic Review Of Ocrelizumab For Multiple Sclerosis

Objective: To access the efficacy and safety of Ocrelizumab in patients with PPMS or RRMS.Methods: After the purpose was confirmed,the English retrieval keywords "multiple sclerosis","MS","RRMS","RMS","PPMS","ocrelizumab","ocrevus","randomized" were extracted,as well as the Chinese retrieval keywords: "multiple sclerosis","ocrelizumab","ocrelizumab","randomized".The English database Cochrane library,Pub Med,Embase,CINAHL,LILACS,Chinese database CNKI,Wan Fang database and other databases were searched according to the search terms to obtain the randomized controlled trials of ocrelizumab in the treatment of multiple sclerosis.The criteria for the search also include a consistent time span(from database construction until October2018),consistent inclusion and exclusion criteria,and no language restrictions.A total of 3 trials(including 2 randomized controlled trials of ocrelizumab for recurrent multiple sclerosis and 1 randomized controlled trial of ocrelizumab for primary progressive multiple sclerosis)were included in the search.The quality and risk of the three trials were analyzed and evaluated,and the data of three trials were analyzed by using Revman5.3 software.Result: In this study,three randomized controlled trials related to ocrelizumab were included,OPERA I and OPERA II of ocrelizumab in the treatment of relapsing-remiting multiple sclerosis,and ORATORIO in the treatment of primary progressive multiple sclerosis.In OPERA I,there are 410 patients in the ocrelizumab group,411 in the interferon group.In OPERA II,there are 417 patients in the ocrelizumab group and 418 patients in the interferon group.Meta analysis results showed that: Disease relapse rate(recurrence within96 weeks)(OR=0.52 95%CI=0.41~0.65 P< 0.00001),confirmed disability progression(disability progression confirmed at 12 weeks)(OR=0.6395%CI=<0.46~0.86 P= 0.004),The mean number of gadolinium-enhancing lesions per T1-weighted magnetic resonance scan(MRI T1 image at 96 weeks)(OR=0.20 95%CI=0.15~0.27 P< 0.00001),the total mean numbers of new or newly enlarged hyperintense lesions per T2-weighted MRI scan(T2 images of MRI at 96 weeks)(OR=0.39 95%ci =0.32~0.48 P< 0.00001),the percentage change in brain volume(MD=0.14 95%ci = 0.05 ~0.23 P< 0.003),and the change in the Multiple Sclerosis Functional Composite score(96 weeks)(MD=0.07 95%ci = 0.02 ~0.13 P= 0.01).All of the above results indicated that there is statistically significant difference in efficacy between ocrelizumab group and interferon group.In the following outcome indicators,the number of patients with at least one adverse event(RR= 1.00 95%ci =0.96~ 1.04 P= 0.96)and the number of patients with severe adverse event(RR=0.79 95%ci =0.57~1.11 P=0.17).The above results indicated that there is no statistically significant difference in safety between the ocrelizumab group and the interferon group.In the ORATORIO trial there are 488 people in the ORATORIO group and 244 people in the interferon group.Meta analysis results show that: The number of patients with confirmed disability progression(12 weeks)(OR=0.7595%CI=0.55~ 1.04 P= 0.08),the total volume of brain lesions on T2-weighted MRI(MD=-10.80 95%CI=-13.73~-7.87 P< 0.0001),and the percentage change in brain volume(MD=0.19 95%CI= 0.01 ~0.37 P= 0.04).The change in the SF-36 Physical Component Summary score from baseline to week 120(MD=0.38 95%CI= minus 1.20~ 1.96 P= 0.64).The results indicated that there is no statistically significant difference in efficacy between the ocrelizumab and placebo groups.In terms of safety,the number of patients with at least one adverse event(OR=2.15 95%ci =1.19~ 3.87 P= 0.01)and the number of patients with severe adverse event(OR=0.90 95%ci =0.62~ 1.31 P= 0.57),statistical analysis show that there is significantly difference between the ocrelizumab group and the placebo group.Conclusion: After analysis,it is proved that ocrelizumab is more effective than interferon beta 1a in the treatment of RRMS,but there is no significant difference in safety compared with interferon beta 1a.In the treatment of PPMS,the clinical efficacy and safety of ocrelizumab still need more long-term randomized controlled trials.