ars.els-cdn.com · Web viewSAR, systemic adverse reactions; SD, standard deviation; BMI, body mass index; LTBI, latent tuberculosis infection; ESRD, end-stage renal disease; 3HP,

Supplement.Supplementary Figure S1. The study profile showing number of cases and reasons for

exclusion.

Supplementary Table 1. Demographic characteristics of LTBI cases with and without SARs during preventive therapyAll cases, n=406 3HP regimen, n=293 9H regimen, n=100

With SAR Without SAR With SAR Without SAR With SAR Without SARCase number 66 340 57 236 8 92Mean age (SD) 57.5 (16.3) 54.5 (17.7) 58.6 (16.8) 55.1 (18.7) 52.1 (10.2) 52.9 (14.2)Age <35 years 4 (6.1%) 55 (16.2%) 3 (5.3%) 38 (16.1%) 1 (12.5%) 13 (14.1%) 35~59 years 32 (48.5%) 148 (43.5%) 26 (45.6%) 99 (41.9%) 5 (62.5%) 46 (50%) 60~79 years 22 (33.3%) 105 (30.9%) 20 (35.1%) 71 (30.1%) 2 (25%) 31 (33.7%) >80 years 8 (12.1%) 32 (9.4%) 8 (14%) 28 (11.9%) 0 2 (2.2%)Male 28 (42.4%) 184 (54.1%) 23 (40.4%) 129 (54.7%) 5 (62.5%) 49 (53.3%)Mean BMI (SD) 23.6 (3.7) 24.8 (4.4)* 23.9 (3.9) 24.9 (4.3) 22.4 (2.2) 24.5 (4.7)Smoking history 24 (36.4%) 88 (25.9%) 20 (35.1%) 66 (28%) 4 (50%) 20 (21.7%)Alcohol consumption 5 (7.6%) 20 (5.9%) 4 (7%) 18 (7.6%) 1 (12.5%) 2 (2.2%)Comorbidities Diabetes 11 (16.7%) 42 (12.4%) 7 (12.3%) 30 (12.7%) 3 (37.5%) 10 (10.9%) Malignancies 6 (9.1%) 13 (3.8%) 6 (10.5%) 10 (4.2%) 0 2 (2.2%) ESRD 15 (22.7%) 28 (8.2%)*** 11 (19.3%) 15 (6.4%)** 4 (50%) 11 (12%)* Autoimmune diseases 6 (9.1%) 51 (15%) 3 (5.3%) 15 (6.4%) 3 (37.5%) 34 (37.5%) Immuno-suppressant 6 (9.1%) 65 (19.1%) 1 (1.8%) 14 (5.9%) 5 (62.5%) 49 (53.3%) Organ transplant 4 (6.1%) 17 (5%) 1 (1.8%) 0 2 (25%) 17 (18.5%) Hepatitis 7 (10.6%) 29 (8.5%) 4 (7%) 16 (6.8%) 3 (37.5%) 13 (14.1%)

With DOPT 57 (86.4%) 257 (75.6%) 57 (100%) 236 (100%) 0 13 (14.1%)3HP regimens 57 (86.4%) 236 (69.4%)**

SAR, systemic adverse reactions; SD, standard deviation; BMI, body mass index; LTBI, latent tuberculosis infection; ESRD, end-stage renal disease; 3HP, three months of once-weekly rifapentine and isoniazid; 9H, nine months of daily isoniazid; and DOPT, direct observed preventive therapy.*p<0.05; **p<0.01; ***p<0.001

Supplementary Table 2. The occurrence of SARs and liver function impairment in older and younger LTBI cases with various preventive therapy regimensa

3HP 9H 4R≥ 60 years < 60 years ≥ 60 years < 60 years ≥ 60 years < 60 years

Case number 127 166 35 65 5 8Occurrences of SARs 28 (22.0%) 29 (17.5%) 2 (5.7%) 6 (9.2%) 0 1 (12.5%)SAR types

Gastrointestinal reactionAbdominal pain 1 (0.8%) 4 (2.4%) 0 0 0 0Nausea/vomiting 8 (6.3%) 9 (5.4%) 0 0 0 0Anorexia 5 (3.9%) 5 (3.0%) 0 1 (1.5%) 0 0

Flu-like symptomsFatigue 11 (8.7%) 10 (6.0%) 1 (2.9%) 3 (4.6%) 0 1 (12.5%)Dizziness 10 (7.9%) 5 (3.0%) 0 5 (7.7%) 0 1 (12.5%)Headache 5 (3.9%) 9 (5.4%) 1 0 0 0Fever 4 (3.1%) 10 (6.0%) 0 0 0 0Myalgia/arthralgia 5 (3.9%) 10 (6.0%) 0 0 0 1 (12.5%)

Hypersensitivity reaction 4 (3.1%) 3 (1.8%) 0 1 (1.5%) 0 0Other drug reactions 0 2 (1.2%) 0 0 0 0

Elevated liver enzymesb

Any 6 (4.7%) 20 (12.0%) 5 (14.3%) 8 (12.3%) 0 0 1~3 ULN 6 (4.7%) 15 (9.0%) 5 (14.3%) 5 (7.7%) 0 0

3~5 ULN 0 4 (2.4%) 0 2 (3.1%) 0 0 >5 ULN 0 1 (0.6%) 0 1 (1.5%) 0 0Jaundicec

Any 4 (3.2%) 5 (3.0%) 1 (2.9%) 0 0 0 1.5~3 mg/dL 3 (2.4%) 5 (3.0%) 0 0 0 0 >3 mg/dL 1 (0.8%) 0 1 (2.9%) 0 0 0Hepatotoxicityd 0 2 (1.2%) 1 (2.9%) 2 (3.1%) 0 0

aData are presented as n (%) unless otherwise stated.bDefined as the highest serum level of alanine aminotransferase (ALT or SGPT) during treatment periodcDefined as the highest serum level of total bilirubin during treatment period.dDefined as AST >3 upper limit of normal (ULN) with symptoms of nausea, vomiting, fatigue or jaundice, or AST >5 × ULN.SARs, systemic adverse reactions and ULN, upper limit of normal; 3HP, three months of once-weekly rifapentine and isoniazid; 9H, nine months of daily isoniazid; 4R, four months of daily rifampicin.

Supplementary Table 3. Demographic characteristics of LTBI cases with and without treatment interruptionAll cases, n=406 3HP regimen, n=293 9H regimen, n=100

With treatment interruption

Without treatment interruptoin

With treatment interruption

Without treatment interruptoin

With treatment interruption

Without treatment interruptoin

Case number 74 332 43 250 29 71Mean age (SD) 58.2 (18.2) 54.2 (17.3) 61.2 (18.8) 54.9 (18.1)* 53.8 (16.8) 52.4 (12.5)Age <35 years 6 (8.1%) 53 (16%) 1 (2.3%) 40 (16%)** 5 (17.2%) 9 (12.7%) 35~59 years 32 (43.2%) 148 (44.6%) 18 (41.9%) 107 (42.8%) 13 (44.8%) 38 (53.5%) 60~79 years 24 (32.4%) 103 (31%) 13 (30.2%) 78 (31.2%) 10 (34.5%) 23 (32.4%) >80 years 12 (16.2%) 28(8.4%) 11 (25.6%) 25 (10%) 1 (3.4%) 1 (1.4%)Male 38 (51.4%) 174 (52.4%) 19 (44.2%) 122 (48.8%) 16 (55.2%) 30 (42.3%)Mean BMI (SD) 24.0 (3.4) 24.8 (4.5) 23.9 (3.1) 24.8 (4.4) 24.2 (3.7) 24.4 (4.8)Smoking history 23 (31.1%) 89 (26.8%) 15 (34.9%) 71 (28.4%) 7 (24.1%) 17 (23.9%)Alcohol consumption 3 (4.1%) 22 (6.6%) 1 (2.3%) 21 (8.4%) 2 (6.9%) 1 (1.4%)Comorbidities Diabetes 10 (13.5%) 43 (13%) 5 (11.6%) 32 (12.8%) 5 (17.2%) 8 (11.3%) Malignancies 3 (4.1%) 16 (4.8%) 2 (4.7%) 14 (5.6%) 0 2 (2.8%) ESRD 14 (18.9%) 29 (8.7%)** 7 (16.3%) 19 (7.6%) 6 (20.7%) 9 (12.7%) Autoimmune diseases 17 (23%) 40 (12.0%)* 2 (4.7%) 16 (6.4%) 14 (48.3%) 23 (32.4%) Immuno-suppressant 17 (23%) 54 (16.3%) 2 (4.7%) 13 (5.2%) 14 (48.3%) 40 (56.3%) Organ transplant 3 (4.1%) 18 (5.4%) 1 (2.3%) 0 2 (6.9%) 17 (23.9%)

Hepatitis 7 (9.5%) 29 (8.7%) 4 (9.3%) 16 (6.4%) 3 (10.3%) 13 (18.3%)With SARs 28 (37.8%) 38 (11.4%)*** 23 (53.5%) 34 (13.6%)*** 5 (17.2%) 3 (4.2%)*With DOPT 48 (64.9%) 266 (80.1%)** 43 (100%) 250 (100%) 4 (13.8%) 9 (12.7%)3HP regimens 43 (58.1%) 250 (75.3%)**

SD, standard deviation; BMI, body mass index; LTBI, latent tuberculosis infection; ESRD, end-stage renal disease; 3HP, three months of once-weekly rifapentine and isoniazid; 9H, nine months of daily isoniazid; DOPT, direct observed preventive therapy.*p < 0.5; **p < 0.01; ***p<0.001.

Supplementary Table 4. Multivariate analysis of clinical factors associated with SARs

in LTBI cases receiving 3HP and non-3HP regimens*Adusted odds ratio (aOR) and 95% confidence interval (CI) were derived from logistic regression analysisBMI, body mass index; 3HP, three months of once-weekly rifapentine and isoniazid; 9H, nine months of daily isoniazid; ESRD, end-stage renal disease.

3HP regimen, n=293 9H regimen, n=100aOR (95% CI)* P value* aOR (95% CI)* P value*

Age years <35 1.00 - 1.00 - 35~59 3.69 (1.02-13.27) 0.046 7.10 (0.27-187.83) 0.241 60~79 3.61 (0.96-13.61) 0.058 7.02 (0.19-261.35) 0.291 ≥ 80 4.53 (1.03-19.87) 0.045 - -Female 1.82 (0.96-3.43) 0.066 0.70 (0.13-3.88) 0.681BMI<23 1.96 (1.05-3.66) 0.035 3.60 (0.66-19.69) 0.086ESRD 3.36 (1.37-8.27) 0.008 18.74 (1.59-220.50) 0.020Immunosuppressant 0.29 (0.04-2.33) 0.245 5.42 (0.47-63.05) 0.177