Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy

Figures & data

Figure 1 Flowchart of article selection process for Topic 1 (ADR and Health-Related QoL).

Figure 2 Flowchart of article selection process for Topic 2 (ADR and Therapeutics Adherence).

Table 1 Quantitative Studies of Association Between ADR and QoL in MDR-TB Patients

Study Design	Setting	Target	HRQoL Measurement	Summary of Result	Reference
Cross sectional	Johannesburg, South Africa, February 2015-January 2018	DR-TB Patients; ≥ 18 years old (n= 149)	Short Form-36 (SF-36)	Patients with ADR experience were more likely to have lower MCS (aRR 2.24 95% CI 1.53–3.27) and PCS (aRR 1.52 95% CI 1.07–2.18).	Sineke et al, 2019^Citation22
Cross sectional	Namibia, January-April 2015	MDR-TB patients in the final month or had completed the treatment within the past 3 months; aged 17–54 years (n= 36)	Short Form-8 (SF-8)	There was no significant different between patients reporting zero to two ADR (median HRQoL score = 56.8; 44.4–56.8) with those reporting three or more ADR (median HRQoL score = 55.2 (38.6–56.8); (p value = 0.34)).	Sagwa et al, 2016^Citation30
Cross sectional	Belo Horizonte, Brazil. March-December 2015.	Both DR-TB and DS-TB patients, >18 years old (n= 73)	Abbreviated World Health Organization Quality of Life Questionnaire (WHOQOL-Bref)	There were significant association between the type of ADR and HRQoL in univariate analysis (p value =0.016) and in multivariate analysis (p value =0.012).	Valadares et al, 2020^Citation20

Abbreviations: HRQoL, health-related quality of life; ADR, adverse drug reaction; MCS, mental component summary; PCS, physical component summary; aRR, adjusted relative risk; CI, confidence interval; DR-TB, drug resistant tuberculosis; MDR-TB, multi-drug resistant tuberculosis.

Table 2 Quantitative Studies of Association Between ADR and Treatment Adherence or Outcome in MDR-TB Patients

Study Design	Setting	Target	Data Collection	Summary of Result	Reference
Cross sectional	Guizhou, China, January-June 2018	MDR-TB Patients (n= 202)	Pill count, interview	ADR (OR: 2.82, 95% CI:1.41–5.61) were the top predictor of treatment interruption.	Wang et al, 2019^Citation49
Cohort retrospective	Yerevan, Armenia, November 2011	DR-TB patients who initiated treatment from 2005 to 2011 (n= 381)	Ratio of treatment doses received under DOT divided by the number of doses prescribed.	Number of ADR (aRR 1.18, 95% CI 1.09–1.27) was associated with loss to follow up from treatment.	Sanchez-Padilla et al, 2014^Citation46
Retrospective cohort	Oromia region, Ethiopia, November 2012-December 2017	DR-TB patients (n= 406)	Patient records	Drug adverse effect (aHR = 6.1; 95% CI: 2.5, 14.34) were independent predictors of loss to follow up.	Woldeyohannes et al, 2021^Citation52
Case control	Philippines, April-July 2014	DR-TB patients, ≥ 18 years old, started treatment from July-December 2012 (lost to follow-up cases, n=91; control, n= 182)	Interview	Vomit was the only ADR that associated with loss to follow-up in multivariate analysis (OR 1.10 (1.01–1.21), p value 0.03) and reported as the primary reason for stopping treatment.	Tupasi et al, 2016^Citation50
Cross sectional	Kano and Kaduna States, Nigeria, January 2015-June 2016	DS-TB and DR-TB patients, adult (n=390)	Tuberculosis Medication Adherence Questionnaire (TBMAQ)	56.7% reported that side effects of anti TB drugs affected their treatment adherence. Antituberculosis drugs side effects were significant variable in bivariate analysis (p < 0.001), but it was insignificant predictor in multivariate analysis (p = 0.191).	Iweama et al, 2021^Citation53
Cross sectional	Rajkot, India	MDR-TB cases during 2010–2013 (n =125)	Registered data	Defaulter was associated with ADR (χ^2 = 20.214, df = 5, p = 0.001). Treatment adherence was associated with no occurrence of ADR (χ^2 = 18.614, df = 1, p = 0.000).	Dela et al, 2017^Citation54
Retrospective cohort	Metro Manila, Philippines	MDR-TB patients treated from 1999 to 2006 (n=583)	Patient records	Uncontrolled ADR was not significantly associated with defaulter (p = 0.35).	Gler et al, 2015^Citation55
Retrospective cohort	Uganda	MDR-TB patients treated from January 2012-May 2016 (n=227)	Registered data	ADR was not significantly associated with non-adherence (p value = 0.357)	Batte et al, 2021^Citation56
Retrospective cohort	Kerala, Delhi and West Bengal, India	MDR-TB in the three States from January 2009 to December 2011.	Treatment card and registered data	ADR has no significant association with unfavorable outcome (p value = 0.09)	Nair et al, 2017^Citation57

Abbreviations: HRQoL, health-related quality of life; ADR, adverse drug reaction; MCS, mental component summary; PCS, physical component summary; aHR, adjusted hazard ratio; OR, odds ratio; CI, confidence interval; DR-TB, drug resistant tuberculosis; MDR-TB, multi-drug resistant tuberculosis.

Figure 3 Illustration of burden of ADR and its impact to QoL and adherence.

Abbreviations: HRQoL, health-related quality of life; ADR, adverse drug reaction; → associated.

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