Frequency and Management of Adverse Drug Reactions Among Drug-Resistant Tuberculosis Patients: Analysis From a Prospective Study

Abstract

Drug-resistant tuberculosis (DR-TB) management is often linked with a higher rate of adverse drug reactions (ADRs) needing effective and timely management of these ADRs, which, if left untreated, may result in a higher rate of loss to follow-up of drug-resistant patients.Study objective: The study was aimed at prospectively identifying the nature, frequency, suspected drugs, and management approaches for ADRs along with risk factors of ADRs occurrence among DR-TB patients at Nishtar Medical University, Hospital, Multan, Pakistan.Materials and Methods: The prospective study included all the DR-TB patients enrolled for treatment from January 2016 to May 2017 at the study site. Patients were evaluated for the treatment-induced ADRs as per standard criteria of the National Tuberculosis Program, Pakistan. Multivariate logistic regression was used to assess the independent variables associated with the occurrence of ADRs.Results: Out of 271 DR-TB patients included in the final analysis, it was observed that 55 patients (20.3%) experienced at least three ADRs. A total of 50 (18.5%) patients experienced zero adverse effects, while 15 (5.5%), 33 (12.2%), and 53 (19.6%) patients experienced one, two, and four ADRs, respectively. Gastrointestinal disturbances (66.7%), nervous system disorders (59.4%), and electrolyte disturbances (55.7%) remained the highest reported ADRs during therapy, followed by arthralgia (49.1%), ototoxicity (24%), pruritic reactions/rash (12.9%), dyspnoea (12.5%), and tinnitus (8.8%). Pulmonary cavitation at the baseline visit (p-value 0.001, OR 3.419; 95% CI (1.694–6.902) was significantly associated with the occurrence of ADRs among DR-TB patients.Conclusion: The frequency of ADRs was high among the study cohort; however, these were managed effectively. Patients with recognized risk factors for ADRs occurrence need continuous clinical management efforts.

Safety Profile of Medicines Used for the Treatment of Drug-Resistant Tuberculosis: A Descriptive Study Based on the WHO Database (VigiBase®)

“…In the present study, vomiting was the most frequently reported ADR, followed by arthralgia, nausea, neuropathy peripheral, and prolongation of electrocardiogram QT, a finding that is more or less similar to the findings from previous studies [20,[26][27][28]. The same sets of ADRs were also reported in a four-year retrospective study conducted by Arif et al [29].…”

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan

“…In our study, 44% patients exhibited psychiatric symptoms. This falls within the range of psychiatric symptoms prevalence reported in studies conducted in Pakistan (29.3-59.4%) (Ahmad, Javaid, et al, 2018 ; Atif et al, 2022 ; Massud et al, 2022 ), but it is higher than the rates reported in studies conducted in Estonia, Latvia, Peru, the Philippines, and the Russian Federation (9.5%) (Nathanson et al, 2004 ), China (12.9%) (Zhang et al, 2017 ), and Russia (20.5%) (SS Shin et al, 2007 ). In addition to toxic effects of SLD, particularly Cs, on the central nervous system (Lan et al, 2020 ), factors such as fatigue and adverse outcomes of the previous episodes of TB treatment (85.3% patients in the current cohort were previously been treated for TB) (Nafees Ahmad et al, 2016 ), along with patients’ poor socioeconomic conditions and the severe nature of the disease itself may have contributed to the relatively higher incidence of psychiatric manifestations in the current cohort (Ahmad, Javaid, et al, 2018 ).…”

“…The incidence of hypothyroidism in this cohort (21.5%) was higher than that reported by studies conducted in Pakistan (1.5%) (Massud et al, 2022 ), Turkey (1.1%) (Törün et al, 2005 ) and Peru (10%) (Furin et al, 2001 ). However, a comparable (19.1%) and relatively higher incidence (36%) of hypothyroidism among MDR-TB patients has been respectively reported from China (Zhang et al, 2017 ) and South Africa (Brust et al, 2013 ).…”

“…Despite the high prevalence of these AEs, only GI disturbance led to a temporary discontinuation of PAS in three patients. Ototoxicity was more prevalent (61.4%) (tinnitus = 19.2% and hearing loss = 42.2%) in our study compared to the reported range in other studies conducted in Pakistan (8.9-24%) (Ahmad, Javaid, et al, 2018 ; Atif et al, 2022 ; Massud et al, 2022 ), elsewhere (5.9-41.8%) (Bloss et al, 2010 ; Ngoc et al, 2021 ; SS Shin et al, 2007 ; Törün et al, 2005 ; Zhang et al, 2017 ) and by a systematic review (28.3%) (Wrohan et al, 2021 ). Nevertheless, despite its high incidence, ototoxicity resulted in modification of the TB treatment regimen in only 12 patients.…”

“…At these centres, MDR-TB patients receive care according to uniform protocols recommended by the World Health Organization (WHO) and adopted by the National TB Control Program (NTP) (Abubakar, Ahmad, Atif, Khan, & Ghafoor, 2022 ; Javaid et al, 2018 ; Khan et al, 2019 ; Naz et al, 2021 ). While there is significant information available from Pakistan regarding the treatment outcomes and predictors of unsuccessful outcomes among MDR-TB patients (Abubakar et al, 2021 ; N Ahmad et al, 2015 ; Atif et al, 2017 ; Javaid et al, 2018 ; Javaid, Shaheen, et al, 2017 ; Khan et al, 2019 ; Naz et al, 2021 ; Abdul Wahid et al, 2022 ), there is scarcity of detailed information regarding the occurrence and management of AEs during MDR-TB treatment as well as their impact on treatment outcomes (Atif et al, 2022 ; Massud et al, 2022 ) from Pakistan in general and Balochistan in particular, which is the largest province in Pakistan in terms of area. Since early detection, monitoring, and appropriate management of AEs are crucial for optimising MDR-TB treatment, therefore, the current study was conducted with the objectives to evaluate the pattern, frequency, management, and risk factors associated with AEs and as well as their impact on treatment outcomes among MDR-TB patients.…”