Title: INCIDENCE AND PREDICTORS OF MAJOR ADVERSE DRUG EVENTS AMONG DRUG-RESISTANT TUBERCULOSIS PATIENTS ON SECOND-LINE ANTI-TUBERCULOSIS TREATMENT IN AMHARA REGIONAL STATE PUBLIC HOSPITALS; ETHIOPIA: A RETROSPECTIVE FOLLOW-UP STUDY; 2010-2017

Background: An adverse drug event is any untoward medical occurrence in a patient administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Second line anti tuberculosis drugs are complex, long term and more toxic. Poor treatment outcome due to adverse drug events become major public health problem globally. Limited evidence is available on incidence and predictors of adverse drug events associated with these drugs in Ethiopia. Thus, this study assessed the incidence and predictors of major adverse drug events among drug resistant tuberculosis patients on second line anti-tuberculosis treatment in Amhara Regional State public hospitals, Ethiopia

Methods: An institution based retrospective follow up study was conducted on 570 Drug Resistant tuberculosis Patients (DR-TB). Data were entered to EPI-Data version 4.2.0.0 and exported to Stata version 14 for analysis. Proportional hazard assumption was checked. The univariate Weibull regression gamma frailty model was fitted. Cox-Snell residual was used to test goodness of fit and AIC for model selection. Hazard ratio with 95% CI was computed and variables with P-value <0.05 in the multivariable analysis were taken as significant predictors for adverse drug event.

Results: A total of 570 patients were followed for 5045.09 person-month (PM) observation with a median survival time of 8.23 months (IQR=2.66-23.33).  The overall incidence rate of major adverse drug event was 5.79 events per 100 PM (95% CI: 5.16, 6.49). Incidence rate at the end of 2^nd, 4th, 6^th months was 13.73, 9.25, 5.97 events per 100 PM observation, respectively. Age (25-49) years (AHR= 3.36, 95%CI: 1.36, 8.28) and above 50 years (AHR= 5.60, 95%CI: 1.65, 19.05) respectively, co-morbid conditions (AHR= 2.74 CI: 1.12, 6.68) and anemia (AHR= 3.25 CI: 1.40, 7.53) were significantly associated with occurrence of major adverse drug event.

Conclusions/Recommendations: The incidence rate of adverse drug events in the first two to six months of treatment was higher than the subsequent months.Older age, base line anemia, and co-morbid conditions were independent risk factors associated with the occurrence of adverse drug events. Thus, addressing the significant predictors and strengthening continuous follow-up is highly recommended in the study setting.

Keywords: Adverse drug event, DR-TB patients, second-line drugs