Safety and Disease Evolution of Fixed-Dose Combination of Antitubercular Treatment Compared to Separate-Drugs Preparation in Extra-Pulmonary Tuberculosis

Abstract

Extra-pulmonary tuberculosis (EPTB) treatment was previously based on separate-drugs preparation (SDP). In the hope of reducing the rates of treatment default and resistance, the WHO have recommended the use of fixed-dose combination (FDC) for first-line in EPTB. We aimed to compare the tolerance and the disease evolution between FDC and SDP regimens in EPTB patients. We conducted a retrospective study including 388 cases of EPTB hospitalized between 1996 and 2016. We compared anti-tuberculosis treatment outcomes and the disease evolution between patients receiving FDC and those receiving SDP. The main EPTB site was lymph node (39.2%). There were no statistical differences between the two groups in terms of musculoskeletal, hematological disorders, cutaneous events, and hepatotoxicity. We noted that neurological disorder (OR = 12; p < 0.001), notably paresthesia (OR = 16; p < 0.001), and retrobulbar neuritis (OR = 10; p = 0.006), as well as gastro-intestinal intolerance (OR = 4; p = 0.015) including nausea (OR = 8.9; p = 0.011) and vomiting (OR = 1.1; p = 0.005) were significantly more frequent in the SDP group. The disease evolution comparison showed that complicated forms were statistically more frequent in the SDP group than those in the FDC group (OR = 2.4; p = 0.003), while there was no significant difference in relapse, sequelae, and death frequencies between the two groups. SDP tolerance was characterized by higher frequency of paresthesia, retrobulbar neuritis, nausea, and vomiting than FDC. Evolutionary profiles were similar, except a higher risk of complicated forms in SDP.