PHASA Conference 22-29 September 2016 Poorer Health-Related Quality of Life Among Patients Who Report Adverse Events while on Treatment for Drug-Resistant TB in Johannesburg, South Africa   Denise Evans, Tembeka Sineke, Kate Schnippel, Helena van Aswegen, Rebecca Berhanu, Lawrence Long, Elisabeth Lönnermark, Sydney Rosen PHASA Conference 22-29 September 2016 PHASA Confere nce 22-29 September 2016

Background South Africa bears a disproportionate share of the world’s epidemic of drug-resistant tuberculosis (DR-TB). Adverse events are common during treatment of DR-TB. Some harm quality of life (e.g. abdominal pain, nausea) Some are disabling (e.g. irreversible hearing loss) Some are life threatening (e.g. renal failure, psychosis, seizures). Little is known about health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of adverse events on HRQoL.

Aims Measure the HRQoL of DR-TB patients receiving outpatient treatment and care using a standardized tool (Short Form 36 Health Survey). Describe the experience of adverse events (AEs) by patients receiving DR-TB treatment including frequency and characteristics of AEs using a standardized tool. Compare health-related quality of life among DR-TB patients who reported an adverse event versus those who do not report an adverse event in the past 4 weeks.

Methods Cross-sectional survey of a sub-sample of patients enrolled in a prospective cohort study. Cohort study enrolled adult (≥ 18) patients who: Documented laboratory diagnosis of RIF resistant TB. Initiated DR-TB treatment at the specialized, outpatient TB Focal Point (FP) of Helen Joseph Hospital, Johannesburg, South Africa after March 2013. Provide informed consent for medical file review. Sample for HRQoL survey: Conveniently sampled patients enrolled in cohort study after February 2015. Willing to participate and provide informed consent. Outcome: Poor HRQoL defined as a low Mental Component Score (MCS) or Physical Component Score (PCS): according to scoring instructions and using the median as a cut-off point.

Methods (Continued) Survey instruments Statistical analysis SF-36, questionnaire asking about health-related quality of life in the past 4 weeks. Part A: All patients, recent symptoms in past four weeks. Part B: Detailed questions about specific AEs reported in Part A (e.g. hearing loss, psychosis or depression, vertigo, and/or (iv) peripheral neuropathy) Part C: Validated hearing loss screening tool (HHIE-S) for patients who reported hearing loss in Part A. Statistical analysis Log-binomial regression was used to test the association between reporting an adverse event in the last four weeks and a low MCS or PCS. Models adjusted for age, gender, and time on DR-TB treatment. Scales were compared to SF-36 scales for healthy adults in Johannesburg from a published study (van Aswegen et al, 2011).

Characteristics of Patients with Drug-Resistant Tuberculosis Description   (N=57) Gender Male Female n, % 33 (57.9%) 24 (42.1%) Age, years ≤35 >35 Median, IQR 37 (29-40) 26 (45.6%) 31 (54.6%) Education Primary/no education Higher 47 (82.5%) 10 (17.5%)  Employment Employed Not Employed 35 (61.4%) 22 (38.6%) Classification RR-TB MDR-TB n,% 42 (73.7%) 15 (26.3%) Time on TB treatment, months 15.6 (8.5 - 20.2) HIV status Positive Negative 49 (86.0%) 8 (14.0%) Baseline CD4 (n=35) 78 (29 - 233) On ART at start of RR-TB treatment Yes No 21/49 (42.9%) 28/49 (57.1%) Time on ART treatment, months 20.6 (10.5 - 29.8)

Adverse Events, Stratified by Age Category More than a third of patients (21/57, 37%) reported an adverse event in the past four weeks. Total of 24 adverse events described: 7 hearing loss, 2 psychosis or depression, 5 vertigo, and 10 peripheral neuropathy. Some patients reported more than 1 adverse events

SF-36 Scales and Mental and Physical Health Component Summary Scores Adverse event not reported (n=36) Adverse event reported (n=21) P value Mean SD Alpha* Physical functioning 94.7 11.7 0.868 72.1 30.3 0.872 0.0004 Role physical 82.6 29.8 0.839 45.2 45.8 0.837 0.001 Role emotional 80.6 35.9 0.836 30.5 0.854 Energy/vitality 64.7 18.1 0.835 50.5 21.8 0.855 0.009 Emotional well-being 72.6 16.6 0.818 58.1 16.8 0.843 0.002 Social functioning 80.2 25.4 0.830 60.7 23.1 0.849 Pain 84.4 23.5 0.820 69.1 26.7 0.858 0.030 General health 75.7 13.1 0.844 68.8 12.5 0.882 0.041 Norm-based scale Mental health component summary (MCS) 46.2 11.4 n/a 33.3 12.3 Physical health component summary (PCS) 55.4 5.8 48.4 9.2 0.007

Summary Scores Patients who reported an adverse event (n=21) had significantly lower scales for physical functioning, emotional role, energy, and social functioning and were more likely to have a lower MCS and PCS. Proportion with lower MCS Crude RR and 95% CI Adjusted RR and 95% CI No adverse event 12/36 1.0 (reference) Adverse event 16/21 3.3 (1.40 – 7.82) 3.7 (1.62– 8.62) Proportion with lower PCS Crude RR and 95% CI Adjusted RR and 95% CI No adverse event 14/36 1.0 (reference) Adverse event 15/21 2.4 (1.09 – 5.33) 2.6 (1.19 – 5.69) After adjusting for age and gender, the association remains with patients who reported an adverse event were more likely to have lower MCS and PCS

SF-36 Scales for Patients on DR-TB Treatment and Healthy Adults When we compare SF-36 scare for Patients on DR-TB Treatment and Healthy Adults, patients with adverse had poor HRQoL compared to healthy patients

Conclusions Patients who reported an adverse event during DR-TB treatment reported poorer HRQoL (MCS and PCS) than those who did not. Based on the SF-36 scales, patients with adverse events reported much poorer HRQoL than healthy adults. These findings are likely to have implications for patients’ clinical, social and economic wellbeing. Study had several limitations: Small sample size – continuing to enroll patients until December 2016. Did not have a comparison group that was representative of study population. Study population has high rates of HIV co-infection (86%), with more complicated HIV/ART cases.

Next steps… SF-36 could be used as a screening tool to identify patients who require referral (e.g. depression or hearing loss) or targeted interventions. We plan to assess whether patients with poor HRQoL, in particular those with poor MCS or poor PCS, have poorer treatment outcomes (e.g. treatment failure, LTFU) and identify which patients may require rehabilitation (e.g. hearing loss) after treatment. We plan to enroll comparison cohorts. Talk about new amendment to look at patients from other sites

Acknowledgments Denise Evans Sydney Rosen Lawrence Long Tembeka Sineke Kathryn Schnippel Heleen van Aswegen Rebecca Berhanu Elisabet Lönnmark Patients and staff at CHRU and Themba Lethu Clinic – Helen Joseph Hospital Talk about new amendment to look at patients from other sites with differ This presentation was made possible by the generous support of the American people through Cooperative Agreement AID 674-A-12-00029 from the United States Agency for International Development (USAID). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government