Table 3.
Stratified analysis of the reporting odds ratio for the lopinavir-ritonavir compared to other drugs in COVID-19 casesa
| Comparison | No. of liver injury/No. of other ADEs | Reporting odds ratio (95% CI) |
Chi-squared test statistic (p-value) | |
|---|---|---|---|---|
| Lopinavir-ritonavir | Comparator | |||
| Drug-induced liver injuryc | ||||
| Lopinavir-ritonavir vs all other drugsb | ||||
| Age < 65 years | 177/216 | 1,687/6,872 | 3.34 (2.72, 4.10) | 146.20 (< 0.0001) |
| Age > = 65 years | 125/260 | 1,050/6,230 | 2.85 (2.28, 3.57) | 91.73 (< 0.0001) |
| Male | 223/332 | 1,891/8,220 | 2.91 (2.44, 3.48) | 152.72 (< 0.0001) |
| Female | 79/154 | 889/5,990 | 3.46 (2.61–4.57) | 84.38 (< 0.0001) |
| Within the United States | 5/14 | 1,831/9,679 | 1.89 (0.68, 5.24) | 1.53 (0.22) |
| Outside of the United States | 308/518 | 1,281/6,160 | 2.86 (2.45, 3.33) | 192.93 (< 0.0001) |
| Lopinavir-ritonavir vs hydroxychloroquine/chloroquine | ||||
| Age < 65 years | 146/141 | 1,414/5,099 | 3.73 (2.94, 4.74) | 132.22 (< 0.0001) |
| Age > = 65 years | 99/194 | 936/5,086 | 2.77 (2.16, 3.57) | 67.88 (< 0.0001) |
| Male | 175/239 | 1,629/6,356 | 2.86 (2.33, 3.50) | 111.62 (< 0.0001) |
| Female | 70/100 | 765/4,874 | 4.46 (3.26, 6.11) | 102.19 (< 0.0001) |
| Within the United States | 3/9 | 1,718/8,643 | 1.68 (0.45,6.20) | 0.61 (0.43) |
| Outside of the United States | 246/362 | 896/3,663 | 2.78 (2.33, 3.32) | 134.90 (< 0.0001) |
| Lopinavir-ritonavir vs remdesivir | ||||
| Age < 65 years | 176/213 | 681/5,468 | 6.63 (5.35, 8.23) | 8.06 (0.0045) |
| Age > = 65 years | 124/259 | 368/4,534 | 5.90 (4.64, 7.49) | 260.23 (< 0.0001) |
| Male | 222/329 | 736/6,327 | 5.80 (4.81, 6.99) | 414.61 (< 0.0001) |
| Female | 78/152 | 323/4590 | 7.29 (5.42, 9.80) | 228.42 (< 0.0001) |
| Within the united states | 3/11 | 294/6,814 | 6.32 (1.75, 22.78) | 10.46 (0.0012) |
| Outside of the united states | 308/516 | 1,068/5,619 | 3.14 (2.69, 3.67) | 224.67 (< 0.0001) |
| Severe drug-induced liver injuryd | ||||
| Lopinavir-ritonavir vs all other drugs | ||||
| Age < 65 years | 72/216 | 399/6,872 | 5.74 (4.32, 7.64) | 180.52 (< 0.0001) |
| Age > = 65 years | 15/260 | 166/6,230 | 2.17 (1.26, 3.73) | 8.17 (0.0043) |
| Male | 66/332 | 431/8,220 | 3.79 (2.86, 5.02) | 98.65 (< 0.0001) |
| Female | 21/154 | 144/5,990 | 5.67 (3.49, 9.21) | 62.24 (< 0.0001) |
| Within the united states | 0/14 | 106/9,665 | NA | NA |
| Outside of the united states | 90/518 | 566/6,160 | 1.89 (1.49, 2.40) | 27.93(< 0.0001) |
| Lopinavir-ritonavir vs hydroxychloroquine/chloroquine | ||||
| Age < 65 years | 61/141 | 262/5099 | 8.42 (6.08, 11.65) | 228.03(< 0.0001) |
| Age > = 65 years | 13/194 | 128/5086 | 2.66 (1.48, 4.80) | 11.50 (0.0007) |
| Male | 56/239 | 298/6356 | 5.00 (3.65, 6.84) | 122.92(< 0.0001) |
| Female | 18/100 | 102/4874 | 8.60 (5.02, 14.74) | 87.37 (< 0.0001) |
| Within the united states | 0/9 | 101/8643 | NA | NA |
| Outside of the united states | 75/362 | 366/3663 | 2.07 (1.58, 2.72) | 28.91 (< 0.0001) |
| Lopinavir-ritonavir vs remdesivir | ||||
| Age < 65 years | 72/213 | 337/5468 | 5.48 (4.11, 7.32) | 164.17 (< 0.0001) |
| Age > = 65 years | 15/259 | 124/4534 | 2.12 (1.22, 3.67) | 7.47 (0.0063) |
| Male | 66/329 | 359/6327 | 3.54 (2.66, 4.70) | 85.00 (< 0.0001) |
| Female | 21/152 | 107/4590 | 5.93 (3.61, 9.72) | 63.39 (< 0.0001) |
| Within the united states | 0/11 | 34/6814 | NA | NA |
| Outside of the united states | 90/516 | 518/5619 | 1.89 (1.49, 2.41) | 27.63 (< 0.0001) |
ADEs adverse drug events, SMQ standardized medical dictionary for regulatory activities query, NA not applicable
aMedDRA preferred terms related to COVID-19 including "asymptomatic COVID-19", "COVID-19", "COVID-19 pneumonia", "suspected COVID-19", "SARS-COV-2 carrier", "exposure to SARS-COV-2", "occupational exposure to communicable disease", "occupational exposure to SARS-COV-2", "coronavirus test", "coronavirus test negative", "SARS-COV-2 test", "SARS-COV-2 test false negative", "SARS-COV-2 test negative", "SARS-COV-2 test positive", "COVID-19 prophylaxis", "COVID-19 treatment", "COVID-19 immunisation", "patient isolation", "quarantine", "multisystem inflammatory syndrome in children", "SARS-COV-2 sepsis", "SARS-COV-2 viraemia", "SARS-COV-2 test false positive", "SARS-COV-2 antibody test"
ball other drugs including the all drugs except lopinavir-ritonavir used in the COVID-19 cases
cidentified by a narrow SMQ of “Drug related hepatic disorders,” which includes narrow scope of cholestasis and jaundice of hepatic origin, liver related investigations, signs and symptoms, liver-related coagulation and bleeding disturbances, noninfectious hepatitis, hepatic failure, fibrosis, cirrhosis, other drug-related liver damage, liver neoplasms (benign, including cysts and polyps), and liver neoplasms (malignant and unspecified)
d identified by a narrow SMQ of “Drug related hepatic disorders—severe events only,” which includes narrow scope of noninfectious hepatitis, hepatic failure, fibrosis, cirrhosis, other drug-related liver damage, liver neoplasms (benign, including cysts and polyps), and liver neoplasms (malignant and unspecified)