Anti-TB Drug-Induced Rush and Leukopenia: Implications for Management of TB-Experience in Japan

Abstract

SESSION TITLE: Tuberculosis SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To investigate the incidence rates and risk factors of rush and leukopenia caused by anti-tuberculous chemotherapy. METHODS: All the patients with active tuberculosis and nontuberculous mycobacteriosis (NTM) , who were treated with anti-tuberculous chemotherapy in our hospital between March 2012 and June 2015. The definition of rush is as follows : rush emerging after induction of anti-tuberculous therapy and suspected to be induced by antituberculous drug. The definition of leukopenia is as follows: decreased white blood cell count (WBC), that is less than 3500/mm3 during chemotherapy, based on CTCAE ver4.0. 220 patients with tuberculosis (including 31 latent tuberculosis infection(LTBI) patients)and 180 patients with nontuberculous mycobacteriosis (including 180 Mycobacterium avium complex (MAC) patients) were analyzed for this study. 116 patients with tuberculosis were treated by isoniazid(INH),rifampicin(RFP),ethambutol(EB) and pyrazinamide(PZA)(HREZ) and 44 patients with tuberculosis were treated by INH,RFP and EB(HRE). 148 patients with MAC were treated by clarithromycin(CAM), RFP and EB(RE-CAM). We examined the incidence rates of rush and leukopenia in patients treated by HREZ, HRE and RE-CAM. Those patients were divided into the rush, non-rush groups and the leukopenia, non-leukopenia groups. We executed multivariate analysis for each factor (age, gender, weight, BMI, pre-treatment WBC, Alb, LDH, T-Bil, AST, ALT, Cre, and CRP, each regimen use). RESULTS: The incidence rates of rush of HREZ, HRE and RE-CAM were 41%, 31%, 33%.There were no significant difference among regimens and factors. The number of cases, in which the responsible drugs for rush was identified, were: 22 cases for EB, 3 cases for INH, 1 case for RFP, and 1 case for PZA. Rush did not require any treatment in 67 cases, although it did antihistaminic agents and external preparation of steroid in 25 cases and desensitization therapy in 16 cases. The incidence rates of leukopenia of HREZ, HRE and RE-CAM were 29%, 31% and 50%. There was a significant difference between RE-CAM and other regimens. (p value 0.02＜0.05). RE-CAM regimen and low WBC count before the treatment were likely to be the risk factors of leukopenia (RE-CAM regimen: Odds ratio 1.690, p value 0.053. low WBC count before the treatment : Odds ratio 0.999, p value 0.000). CONCLUSIONS: Since among HREZ, HRE and RE-CAM regimens including RFP and EB, there was no significant difference in the incidence rates of rash, INH and PZA might be thought to be less potent on emerging of rash. RFP and EB might be the responsible drugs for rash. In this study, EB was the most common drug that was identified. The most responsible drug for leukopenia might be RFP through the data above. RE-CAM regimen might be the riskiest one in inducing leukopenia because inhibition of P-glycoprotein by CAM may elevate the concentration of RFP in blood, enhancing leukopenia by RFP. Fortunately, in the majority of cases with leukopenia, severity was mild (grade1 to 2) and so they could continue treatment without changing the regimen. CLINICAL IMPLICATIONS: It's important to know the resoponsible drug and treatment for rush and leukopenia by anti-tuberculous chemotherapy to continue and complete the treatment. DISCLOSURE: The following authors have nothing to disclose: Shunichi Nishima No Product/Research Disclosure Information