IDDF2019-ABS-0045\u2005Comparison of sequential, incremental and concomitant reintroduction regimens of anti-tubercular therapy(ATT) after initial episode of ATT hepatitis: a systematic review and network meta-analysis

Abstract

Background Various reintroduction regimens are used for reintroducing antitubercular therapy (ATT) in patients who had hepatitis previously related to use of ATT. Reintroduction of ATT in these patients has not been studied systematically. Methods We performed a systematic review and network meta-analysis of randomized trials to compare the safety of three different reintroduction regimens (Incremental, sequential and concomitant) of ATT using R software with ‘gemtc’ package. Articles were retrieved from various databases from inception to 28thDec 2018 with ‘chemical and drug-induced liver injury’, ‘ATT hepatotoxicity’, ‘drug-induced liver injury’ and ‘reintroduction of anti-tubercular drugs’ as search keywords. We excluded the articles published in languages other than English, case reports, case series and narrative reviews. Recurrence of hepatotoxicity after reintroduction of ATT was taken as the primary outcome. We also compared if the sequence of introduction of isoniazid or rifampin affected the risk of ATT hepatitis. The random effect network model was constructed taking logit likelihood function and heuristically imputed outcome scale assuming uniform standard deviation (0,2.615) as heterogeneity prior. The burn in, inference and thinning were kept at 20000, 100000 and 10 respectively. Results We found a total of 71 citations in our systematic search, out of which 4 randomized control trials were found eligible and included in the meta-analysis. The rank probability test of network meta-analysis demonstrated that incremental reintroduction therapy has a high chance of number one in all three regimens. Compared with concomitant regimen, incremental regimen was found better (odds ratio [OR] 0.24; 95% CI 0.017,1.2) then sequential regimen (OR 0.33; 95% CI 0.033,1.7). The point scale reduction factor of both consistency and node-split models was achieved less than 1.05. The deviance information criterion (DIC) and residual deviance of the consistency model were 17.3 and 9.8. Conclusions The sequential and incremental were better than concomitant. The order of reintroduction of rifampin and isoniazid does not seem to make any difference to the recurrence of ATT hepatitis.