Risk And Management For Tuberculosis Infection In Patients With Inflammatory Bowel Disease Receiving Anti-tumor Necrosis Factor Treatment

Background:Infliximab(IFX)therapy increases risk of tuberculosis(TB)infection among patients with inflammatory bowel disease(IBD)including Crohn's disease(CD)and ulcerative colitis(UC),and chemo-prophylaxis as well as TB screening could reduce such risks.China is a country with high TB incidence and yet there's no data available on TB incidence,the status of TB screening before IFX therapy,and the strategy as well as efficacy of TB chemoprophylaxis.Objective:This study investigated the incidence and risk factors for TB activation among IBD patients receiving IFX therapy in China,and also investigated the status of TB screening and efficacy of chemoprophylaxis in China.Methods:All IBD patients undergoing IFX treatment in 18 hospitals nationwide were enrolled retrospectively.General demographic characteristics of patients,clinical diagnosis,smoking,and collecting clinical data of TB screening before IFX therapy,including previous TB history,tuberculin Test(TST test),Interferon-y release test(IGRA)and chest image results,collecting TB screening results as judged by the doctor,the course of IFX treatment and the use of steroids and immunosuppressive agents,clinical data related to prophylactic treatment,and the final investigation of whether active TB occurred and treatment course if occurred were all recorded.The first part investigated the incidence of TB after IFX therapy in IBD patients and explored the risk factors and clinical characteristics of TB.The second part investigates the status of TB screening in IBD patients with IFX therapy in China,including the prevalence of latent TB and the completion status of TB screening.The third part investigated the differences in the outcomes of conventional prophylaxis versus selective prophylaxis anti-TB before initiation of IFX in Chinese patients with IBD,and further explores the anti-TB strategies and drug that are suitable for China.Results:Part ?:Of 1968 IBD patients receiving IFX,with 1779 CD patients and 189 UC patients.Mean time of follow-up was 1.07±0.87 years.The average age was 28.95±11.23 years.Twenty-one patients(19 patients with CD and 2 patients with UC)developed active TB among 1968 patients with IBD.The incidence of TB in the study population was 999.07 per 100,000 person-years,with 1.07%of all IBD patients developed active TB.Incidence of TB was 978.79 per 100,000 person-years for CD and 1243.97 per 100,000 person-years for UC.All active TB cases were pulmonary TB and the average time to TB outbreak since the first IFX infusion was 200 days(IQR 93-284 days).Time to TB outbreak among patients with latent TB infection(LTBI)was shorter than patients without LTBI.LTBI was an independent risk factor for TB activation(OR 5.09,95%CI:[2.24-16.54],p<0.01).Part ?:Screening for TB before IFX treatment showed 166 IBD patients with LTBI and 1802 were non-LTBI.The positive rate of screening was 8.43%(166/1802).The screening status showed that the screening was not sufficient.Among the 1968 patients,81(4.12%)still had no chest imaging screening and 151(7.67%)did not complete any screening for TS? or IGRAs.Combined with TST??IGRA and chest imaging,the detection rate of LTBI is over 90%,and the consistency between TST and IGRAs used for diagnosis LTBI is poor.Part ?;There is no significant difference in the efficacy of routine versus selective prophylactic anti-TB strategies in preventing TB during IFX treatment among patients with IBD in China(1.04%[5/483]vs.0.70%[10/1433],?2=0.18,p=0.67).The incidence of adverse reactions to anti-TB drugs between the two groups was also not statistically significant(9.09%[5/55]vs.5.59%[27/483],?2 = 0.55,p=0.46).Subgroup analysis found that prophylaxis anti-TB reduced the incidence of TB in the LTBI group(2.63%[3/114]vs.11.54%[6/52],?2=3.924,p=0.048),but not in the non-LTBI group(0.71%[3/424]vs.0.65%[9/1378],?2=0,p=1).INH monotherapy for six months among LTBI patients significantly reduced incidence of TB compared to patients without chemoprophylaxis.Conclusion:Part I:IBD patients receiving IFX in China are at risk of TB infection,especially the risk of pulmonary TB.LTBI is an independent risk factor for TB in IBD patients in China.In China,a country with a high TB burden,it is recommended that IBD patients undergo a strict screening for LTBI before IFX therapy.Part ?:The prevalence of LTBI before IFX treatment in IBD patients in China is low and TB screening is not sufficient.The combination of TST?IGRA and chest imaging may be more suitable for IBD patients with IFX therapy in China.Part ?:Prophylactic anti-TB treatment is recommended for patients with IBD who have positive screening for LTBI before IFX treatment,but routine preventive anti-TB for non-LTBI patients who are negative for screening is not recommended.Selective anti-TB prophylaxis strategy and prophylaxis with INH alone for 6 months may be effective and suitable for patients with IBD with IFX therapy in China.