Adverse Drug Reactions to a Daily Fixed-dose Combination Based Antituberculosis Treatment Regime in India’s National Tuberculosis Elimination Programme: A Prospective Cohort Study

Abstract

Introduction: In India, the daily weight-based, Fixed Dose Combination (FDC) Antituberculosis Treatment (ATT) regime under the National Tuberculosis Elimination Programme (NTEP) was introduced, replacing the previous intermittent regime with the aim of improving compliance, decreasing Adverse Drug Reactions (ADRs) and thus ultimately translating to improved treatment outcomes. The ADRs are an important factor that can adversely impact the treatment compliance and outcomes of an ATT regime. There is currently a paucity of studies reflecting the development of ADRs in the Indian population to the new ATT regime. Aim: To study the ADRs of daily FDC-based first-line ATT regime under NTEP. Materials and Methods: A prospective cohort analysis was conducted in the Department of Respiratory Medicine at Indira Gandhi Government Medical College (tertiary care centre), Nagpur, Maharashtra, India, from January 2019 to September 2020. Total 750 People With Tuberculosis (PWTB) were enrolled in the study. They were administered a standardised daily FDC first-line ATT regime under NTEP comprising of initial two months of intensive phase with Isoniazid (INH or H), Rifampicin (R), Ethambutol (E), and Pyrazinamide (Z) followed by a continuation phase of four months with INH, rifampicin, and ethambutol (2EHRZ/4HRE). Clinical evaluation and/or laboratory investigations were used at baseline and when clinically indicated during therapy to identify treatmentrelated adverse events. Results: Among the 750 PWTB, 402 (53.60%) were females, and 348 (46.40%) were males. The mean age of PWTB was 36.46±15.6 years. The ADR to ATT was present in 271 (36.13%) PWTB, 217 (80.07%) were managed on an Outpatient Department (OPD) basis and 54 (19.93%) patients required hospitalisation. Causality assessment revealed that most ADRs were probable (81.18%), followed by possible (18.82%). Regarding the severity of ADRs, 87.08% were mild, 11.44% were moderate, 1.48% were severe, and none of the ADRs was life-threatening. In 67.9% of PWTB, gastrointestinal ADRs were seen, followed by joint pain (37.64%) and cutaneous drug reactions (16.60%). Female PWTB, People Living with Human Immunodeficiency Virus & Tuberculosis (PLHIV-TB), and PWTB with systemic co-morbidities, especially diabetes and systemic hypertension, were at a higher risk of developing ADRs. The risk of ADRs was unaltered with age distribution, body mass index distribution, type of diet, the type of tuberculosis, or the pill burden. Addiction to alcohol and tobacco did not significantly alter the risk of ADRs. Conclusion: The ADRs caused by daily FDC-based ATT are common, but most are mild and can be managed on an OPD basis. Gastrointestinal ADRs, arthralgia, and cutaneous drug reactions are the most common ADRs of the daily FDC-based ATT regime. Female PWTB, PLHIV-TB, and PWTB with systemic co-morbidities, especially diabetes and systemic hypertension, being at a high risk of developing ADRs, need to be actively screened for ADRs during treatment.