The Efficacy Of Immunosuppressants And Infliximab In The Treatment Of IBD: A Meta Analysis

Objective:to assess these randomise controlled trials which manifest the efficacy and side effect of general immunosuppressants and infliximab in the treatment of IBD by meta analysis,to acquaint the efficacy and side effect of these immunosuppressants and infliximab, in order to chose medicine rationall and safely.Methods:Randomise controlled trials(RCTs) which need for this research are searched from controlled trials of cochrane library database,PubMed, Ovid Medline, EMCC, CBM,CNKI, VIP database of Chinese,Articles Database.These literature describe IBD (including UC (ulcerative colitis, UC) and CD (crohn's disease)) patients remission induction and maintenance therapy of seseveral immunosuppre-ssants, including:azathioprine(AZA),6-mercaptopurine(6-MP), methotrexate(MTX), ciclosporinA,tacrolimus,Mycophenolate mofetil(MMF), infliximab.The meta analysis is completed by Revman 4.2.2 software which provided from Cochrane website.Results:There are 45 RCTs meet our criteria and bring into this research.17 studies are relation to azathioprine, including azathioprine compare to placebo or glucocorticoid, azathioprine compare to salicylate,patients who have maintained remission continue to oral azathioprine or not, azathioprine use to treat UC patients or CD patients; 3 studies are 6-mercaptopurine in the treatment of IBD compare to placebo or mesalazine;2 studies are Mycophenolate Mofetil compare to azathioprine,6 studies are ciclosporin A compare to placebo;7 studies are methotrexate compare to placebo or glucocorticoid;3 studies are tacrolimus compare to placebo; 10 studies are infliximab compare to placebo or glucocorticoid.All literature assess remission rate, relapse rate,side effect and so on. All of them are scored by modified Jadad score,used random effect model or fixed effect model depending on whether they heterogeneous.The outcome of meta analysis manifest as follow:①Meta-analysis of azathioprine treatment in IBD:In the UC patients azathioprine is shown to be superior for the maintenance of remission(1 year) as compared to placebo or glucocorticoid (OR=2.54,95%:1.05～6.14).After one year of treatment,the relapse rate is lower in AZA group (OR=0.51,95%:0.3～0.89); In the CD patients, AZA is shown to be superior for the maintenance of remission (7 to 15 months) as compared to placebo or glucocorticoid (OR=4.55,95%:1.90～10.89), the relapse rate is lower in AZA group than in control group (OR=0.27,95%:0.10～0.70);But The number of side effects is more than in placebo group (OR= 5.45,95%:1.81～16.38), The number of patients withdrawal due to side effects compared with placebo trial showed no statistically significant (OR=0.92,95%:0.47～1.82);In the UC patients who maintained remission more than six months,the relapse rate of withdrawal AZA is higher than who don't(OR=0.29,95%:0.09～0.89); In the CD patients who maintained remission more than two years,the relapse rate is higher than who don't withdrawal AZA(OR=0.24,95%:0.08～0.73); Between AZA in the treatment of UC and CD,the efficacy has no significant difference(OR=1.36, 95%:0.93～2.01);AZA compared with salicylic acid drugs in the treatment of IBD:Azathioprine or 6-MP is shown to be superior for achieving remission(6 to 9 months) as compared to salicylic acid drugs(OR=6.07,95%:3.03～12.17), The number of treatment failure is significantly less than the SA group (OR=0.16,95%:0.08～0.32), The number of patients withdrawal due to side effects showed no statistically significant(OR=2.08, 95%:0.98～4.39), but the number of side effects is more in AZA group(OR=3.56,95%:1.56～8.10);②Meta-analysis of 6-mercaptopurine treatment in IBD:compare to placebo or mesalazine,6MP shows to be superior for the maintenance of remission(l to 1.5 year) (OR=9.65,95%:4.26～21.87), The number of side effects compared with placebo has no significant difference(OR=1.92,95%:0.71～5.23);③Meta-analysis of ciclosporinA treatment in IBD:compare to placebo,the efficacy of remission induction(1 week and 12 week) shows no significant difference,1 week (OR=8.28,95%:0.18～372.04),12week(OR= 1.44,95%:0.36～5.77);After 4 to 6 months treatment, ciclosporin shows to be superior for the maintenance of remission as compared to placebo (OR=1.95,95%:1.15～3.32), but the maintenance of remission rate has no significant difference after 1 year(OR=1.21,95%:0.62～2.36);We aslo compared the treatment failure rate at 12-16 weeks and 12-20 months,both have no significant difference,12-16 weeks (OR=0.89,95%:0.60～1.33),12-20months (OR=1.28,95%:0.87～1.88), but The number of patients withdrawal due to side effects and the number of side effects are more than placebo group(OR=29.39,95%:7.53～114.66) and (OR=4.51,95%:2.25～9.03);④Meta-analysis of methotrexate treatment in IBD:in the IBD patients, the efficacy of oral 12.5-15mg/w methotrexate or placebo in the maintenance of remission rate(9months) has no significant difference (OR=0.83,95%:0.4～1.72);In CD patients, the efficacy of oral 12.5-15mg/w methotrexate in the maintenance of remission rate(9-10months)is higher than placebo(OR=3.98,95%:1.71～9.24), the efficacy of oral higher dose 22.5-25mg/w methotrexate in the maintenance of remission rate (4-12months) is also higher than placebo (OR=2.47,95%:1.15～5.34); in UC patients, the efficacy of 12.5-15mg/w methotrexate (8-9month) has no significant difference compare to placeto(OR=1.43,95%:0.61～3.34); Except for nausea and vomiting (OR=2.80,95%:1.63～4.83), other side effects has no significant difference (OR=1.13,95%:0.89～1.43), but The number of patients withdrawal due to side effects is more than placebo group(OR=5.8,95%:1.68～20.11);After 6-9 month treatment of IBD with methotrexate,the maintenance of remission rate compare to AZA or 6MP has no significant difference(OR=0.73, 95%:0.36～1.49), The number of patients withdrawal due to side effects has no significant difference,too(OR=1.09,95%:0.34～3.49),but the number of side effects are higher than AZA or 6MP(OR=3.99,95%:1.64～9.74); We also compared the efficacy of different drug delivery,The efficacy of intramuscular methotrexate is significantly higher than placebo (OR=2.81,95%:1.51～5.25), the efficacy of oral methotrexate has no significant difference (OR=1.80,95%:0.79～4.12);⑤Meta-analysis of tacrolimus treatment in IBD:Treatment in CD patients with tacrolimus for 10-12 weeks, the maintenance of remission rate is higher than placebo group (OR=4.92,95%:1.59～15.19), In UC patients treatment with tacrolimus for 2 weeks, the maintenance of remission rate is higher than placebo group(OR=6.00,95%:1.84～19.59), The number of patients withdrawal due to side effects has no significant difference (OR=1.39,95%:0.4～4.78), but the number of side effects is higher compare to placebo (OR=4.26,95%:1.24～14.26);⑥Meta-analysis of mycophenolate mofetil compare to AZA treatment in IBD:in IBD patients, the maintenance of remission rate (6 month) compare to AZA has no significant difference(OR=0.43,95%:0.15～1.26);⑦Meta-analysis of infliximab treatment in IBD:In UC patients, the effect of treatment with infliximab 5mg/kg (2-3 weeks) showed no significant difference compare to placebo (OR=4.17,95%:0.60～29.16), but after 6-13 weeks and more than 14 weeks,the effect show significant difference compare to placebo,6-13weeks (OR=4.23,95%:3.19～5.62), more than 14weeks (OR=2.85,95%:2.11～3.84); The number of treatment failure less than the placebo group(OR=0.19,95%:0.06～0.61); Infliximab shows to be superior for the remission(8 weeks,30-54weeks) as compared to placebo,8 weeks (OR=3.73,95%:2.26～6.15),30-54weeks (OR=3.45,95%:2.20～5.42), the number of side effects is higher than placebo(OR=1.49,95%:1.02～2.17),In CD patients, the maintenance of remission rate with infliximab 5mg/kg(1 year) is higher than placebo group(OR=2.56,95%:1.59～4.11), the superiority is also shown after treatment with infliximab 10mg/kg for 30 weeks(OR= 3.05,95%:1.69～5.51), the number of side effects has no significant difference(OR=0.90,95%:0.51～1.57);We also compared different doses of infliximab efficacy in IBD patients:,after treatment with infliximab 10mg/kg for 30 weeks, the maintenance of remission rate is higher compare to infliximab 5mg/kg (OR=0.75,95%:0.55～1.02);However, maintenance therapy after 54 weeks,the two groups showed no difference (OR= 0.84,95%:0.57～1.24)Conclusion:Immunosuppressants and infliximab in this study,the efficacy of infliximab for IBD patients is the most significant;In the treatment of CD patients, azathioprine shows efficacy after six months, remission in IBD patients continue to use azathioprine maintenance therapy can reduce the relapse rate significantly,the efficacy of treatment in UC and CD patients shows no significant difference; methotrexate shows obvious efficacy in the treatment of CD patients more than six months,compare to azathioprine or 6-mercaptopurine,the efficacy has no significant difference; azathioprine, methotrexate required a long time to show their effect(4 months to 1 year),but the efficacy for a longer is needed to confirm; the efficacy of cyclosporine in IBD patients remains to be further confirmed; Otherwise, 6-mercaptopurine, mycophenolate mofetil an tacrolimus may be effective for the treatment of IBD, But still need more high-quality RCT studies to support;Because we didn't find RCT studies about cyclophosphamide and thalidomide, so we didn't assess them.The number of several side effects of immunosuppressants in this study is more than placebo(except for mycophenolate mofeti), Therefore, the clinical use of immunosuppressive therapy in IBD patients should also consider the side effects and closely observed the occurrence of side effects...