Why this survey was conducted?
|
Molnupiravir is an oral antiviral drug that received special approval for emergency use in 2021, for infectious disease caused by SARS-CoV-2. |
This PMS was conducted to obtain data regarding the safety and effectiveness of molnupiravir in Japanese patients, obtained under clinical practice. |
What was learned from the survey?
|
This interim analysis is the first report of the safety and effectiveness of molnupiravir in over 1000 patients, reflecting a real-world setting in Japan, and is significant in that it provides detailed large-scale information on the background of patients prescribed molnupiravir in Japan, the actual administration status, safety, and to a limited extent, effectiveness. |
This analysis of molnupiravir in daily clinical practice use in Japan supports the safety and effectiveness profile of molnupiravir in treating COVID-19, under pandemic conditions in which Omicron was the dominant SARS-CoV-2 variant. |
Introduction
Methods
Patient Population
Compliance with Ethics Guidelines
Data Collection and Assessment
Safety Assessments
Effectiveness Assessments
Statistical Analysis
Results
Patient Disposition
Patient Characteristics
Variables | Total (N = 1031) | Inpatient or outpatient at the start of molnupiravir administration | ||
---|---|---|---|---|
Inpatient (N = 294) | Outpatient (N = 689) | Othersa (N = 48) | ||
n (%) | n (%) | n (%) | n (%) | |
Gender | ||||
Male | 547 (53.06) | 144 (48.98) | 391 (56.75) | 12 (25.00) |
Female | 484 (46.94) | 150 (51.02) | 298 (43.25) | 36 (75.00) |
Age (years) | ||||
Median (min, max) | 68.0 (18, 107) | |||
< 18 | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
≥ 18 to < 65 | 431 (41.80) | 83 (28.23) | 348 (50.51) | 0 (0.00) |
≥ 65 | 590 (57.23) | 202 (68.71) | 340 (49.35) | 48 (100.00) |
Unknown/not disclosed | 10 (0.97) | 9 (3.06) | 1 (0.15) | 0 (0.00) |
BMI (kg/m2) | ||||
Median (min, max) | 23.54 (12.9, 65.7) | |||
< 30 kg/m2 | 533 (51.70) | 222 (75.51) | 279 (40.49) | 32 (66.67) |
≥ 30 kg/m2 | 93 (9.02) | 26 (8.84) | 67 (9.72) | 0 (0.00) |
Unknown | 402 (38.99) | 45 (15.31) | 341 (49.49) | 16 (33.33) |
Not reported | 3 (0.29) | 1 (0.34) | 2 (0.29) | 0 (0.00) |
Vaccination against SARS-CoV-2 | ||||
No | 94 (9.12) | 37 (12.59) | 54 (7.84) | 3 (6.25) |
Yes | 862 (83.61) | 232 (78.91) | 586 (85.05) | 44 (91.67) |
Unknown | 75 (7.27) | 25 (8.50) | 49 (7.11) | 1 (2.08) |
Presence of COVID-19 symptoms | ||||
No | 28 (2.72) | 15 (5.10) | 13 (1.89) | 0 (0.00) |
Yes | 1003 (97.28) | 279 (94.90) | 676 (98.11) | 48 (100.00) |
History of COVID-19 | ||||
No | 1026 (99.52) | 293 (99.66) | 685 (99.42) | 48 (100.00) |
Yes | 5 (0.48) | 1 (0.34) | 4 (0.58) | 0 (0.00) |
COVID-19 severity prior to initiation of molnupiravir administration | ||||
Mild | 906 (87.88) | 219 (74.49) | 648 (94.05) | 39 (81.25) |
Moderate I | 99 (9.60) | 58 (19.73) | 33 (4.79) | 8 (16.67) |
Moderate II | 23 (2.23) | 17 (5.78) | 5 (0.73) | 1 (2.08) |
Severe | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
Unknown | 3 (0.29) | 0 (0.00) | 3 (0.44) | 0 (0.00) |
SARS-CoV-2 testing at the initiation of the molnupiravir administration | ||||
No | 72 (6.98) | – | – | – |
Yes | 959 (93.02) | – | – | – |
Test result: positive | 958 (99.90) | – | – | – |
Test result: negative | 0 (0.00) | – | – | – |
Test result: unknown/not reported | 1 (0.10) | – | – | – |
Presence of comorbidities including risk factors for severe COVID-19 illness | ||||
No | 153 (14.84) | 30 (10.20) | 123 (17.85) | 0 (0.00) |
Yes | 863 (83.71) | 264 (89.80) | 551 (79.97) | 48 (100.00) |
Unknown | 15 (1.45) | 0 (0.00) | 15 (2.18) | 0 (0.00) |
Comorbiditiesb, c | ||||
Hypertensiond | 464 (45.00) | 131 (44.56) | 309 (44.85) | 24 (50.00) |
Type 2 diabetes mellitusd/diabetes mellitus | 230 (22.31) | 79 (26.87) | 145 (21.04) | 6 (12.50) |
Dyslipidemiad | 208 (20.17) | 53 (18.03) | 152 (22.06) | 3 (6.25) |
Chronic kidney diseased | 72 (6.98) | 47 (15.99) | 21 (3.05) | 4 (8.33) |
COPD | 53 (5.14) | 27 (9.18) | 26 (3.77) | 0 (0.00) |
Malignant tumor | 49 (4.75) | 27 (9.18) | 20 (2.90) | 2 (4.17) |
Cerebral infarction | 38 (3.69) | 22 (7.48) | 12 (1.74) | 4 (8.33) |
Dementia | 37 (3.59) | 14 (4.76) | 9 (1.31) | 14 (29.17) |
Hyperlipidemia | 37 (3.59) | 5 (1.70) | 30 (4.35) | 2 (4.17) |
Asthma | 36 (3.49) | 3 (1.02) | 32 (4.64) | 1 (2.08) |
Essential hypertension | 34 (3.30) | 6 (2.04) | 28 (4.06) | 0 (0.00) |
Hyperuricemia | 31 (3.01) | 9 (3.06) | 22 (3.19) | 0 (0.00) |
Presence of hepatic dysfunctione at the start of molnupiravir administration | ||||
No | 972 (94.28) | 281 (95.58) | 644 (93.47) | 47 (97.92) |
Yes | 28 (2.72) | 13 (4.42) | 14 (2.03) | 1 (2.08) |
Unknown | 31 (3.01) | 0 (0.00) | 31 (4.50) | 0 (0.00) |
Presence of renal dysfunctione at the start of molnupiravir administration | ||||
No | 953 (92.43) | 265 (90.14) | 642 (93.18) | 46 (95.83) |
Yes | 47 (4.56) | 29 (9.86) | 16 (2.32) | 2 (4.17) |
Unknown | 31 (3.01) | 0 (0.00) | 31 (4.50) | 0 (0.00) |
Presence of pretreatment drugs for COVID-19f | ||||
No | 916 (88.85) | 272 (92.52) | 596 (86.50) | 48 (100.00) |
Yes | 86 (8.34) | 22 (7.48) | 64 (9.29) | 0 (0.00) |
Unknown | 29 (2.81) | 0 (0.00) | 29 (4.21) | 0 (0.00) |
Pretreatment drugs for COVID-19 | ||||
Steroidal drug | 3 (0.29) | 2 (0.68) | 1 (0.15) | 0 (0.00) |
Blood coagulation inhibitors (heparin) | 2 (0.19) | 2 (0.68) | 0 (0.00) | 0 (0.00) |
SARS-CoV-2 neutralizing antibody | 14 (1.36) | 10 (3.40) | 4 (0.58) | 0 (0.00) |
Remdesivir | 3 (0.29) | 3 (1.02) | 0 (0.00) | 0 (0.00) |
Baricitinib | 2 (0.19) | 2 (0.68) | 0 (0.00) | 0 (0.00) |
Other drugs | 69 (6.69) | 9 (3.06) | 60 (8.71) | 0 (0.00) |
Number of times vaccinated against SARS-CoV-2 | ||||
1 | 7 (0.68) | 4 (1.36) | 3 (0.44) | 0 (0.00) |
2 | 657 (63.72) | 179 (60.88) | 436 (63.28) | 42 (87.50) |
3 | 169 (16.39) | 47 (15.99) | 120 (17.42) | 2 (4.17) |
Unknown | 29 (2.81) | 2 (0.68) | 27 (3.92) | 0 (0.00) |
Types of vaccination against SARS-CoV-2b | ||||
Comirnaty | 569 (55.19) | 122 (41.50) | 406 (58.93) | 41 (85.42) |
COVID-19 Vaccine Moderna | 75 (7.27) | 9 (3.06) | 66 (9.58) | 0 (0.00) |
Other | 1 (0.10) | 0 (0.00) | 1 (0.15) | 0 (0.00) |
Unknown | 234 (22.70) | 109 (37.07) | 121 (17.56) | 4 (8.33) |
Not reported | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
Period from the final vaccination against SARS-CoV-2 to initiation of the molnupiravir administration (month)g | ||||
Median (min, max) | 6.0 (−3.0, 10.0) | |||
Presence of concomitant medications for COVID-19h | ||||
No | 661 (64.11) | 153 (52.04) | 466 (67.63) | 42 (87.50) |
Yes | 338 (32.78) | 141 (47.96) | 191 (27.72) | 6 (12.50) |
Unknown | 32 (3.10) | 0 (0.00) | 32 (4.64) | 0 (0.00) |
Concomitant medications for COVID-19c | ||||
Steroidal drug | 42 (4.07) | 36 (12.24) | 5 (0.73) | 1 (2.08) |
Blood coagulation inhibitors (heparin) | 15 (1.45) | 14 (4.76) | 1 (0.15) | 0 (0.00) |
SARS-CoV-2 neutralizing antibody | 142 (13.77) | 118 (40.14) | 22 (3.19) | 2 (4.17) |
Remdesivir | 4 (0.39) | 3 (1.02) | 1 (0.15) | 0 (0.00) |
Baricitinib | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
Other drugsi | 185 (17.94) | 15 (5.10) | 167 (24.24) | 3 (6.25) |
Dialysis treatmentj | ||||
No | 983 (95.34) | 276 (93.88) | 660 (95.79) | 47 (97.92) |
Yes | 22 (2.13) | 18 (6.12) | 4 (0.58) | 0 (0.00) |
Unknown | 26 (2.52) | 0 (0.00) | 25 (3.63) | 1 (2.08) |
Oxygen administration or mechanical ventilation at the start of molnupiravir administrationk | ||||
No | 963 (93.40) | 242 (82.31) | 675 (97.97) | 46 (95.83) |
Yes | 24 (2.33) | 22 (7.48) | 2 (0.29) | 0 (0.00) |
Unknown/not reported | 44 (4.27) | 30 (10.20) | 12 (1.74) | 2 (4.17) |
Risk factors for severe COVID-19 illness | Total (N = 1031) | Inpatient or outpatient at the start of molnupiravir administration | ||
---|---|---|---|---|
Inpatient (N = 294) | Outpatient (N = 689) | Othersa (N = 48) | ||
n (%) | n (%) | n (%) | n (%) | |
Presence of risk factors for severe COVID-19 illness | ||||
No | 33 (3.20) | 9 (3.06) | 24 (3.48) | 0 (0.00) |
Yes | 998 (96.80) | 285 (96.94) | 665 (96.52) | 48 (100.00) |
Number of risk factors | ||||
1 | 323 (31.33) | 82 (27.89) | 238 (34.54) | 3 (6.25) |
2 | 330 (32.01) | 75 (25.51) | 222 (32.22) | 33 (68.75) |
3 | 210 (20.37) | 61 (20.75) | 138 (20.03) | 11 (22.92) |
4 | 93 (9.02) | 38 (12.93) | 54 (7.84) | 1 (2.08) |
5 | 32 (3.10) | 21 (7.14) | 11 (1.60) | 0 (0.00) |
6 | 7 (0.68) | 5 (1.70) | 2 (0.29) | 0 (0.00) |
7 | 3 (0.29) | 3 (1.02) | 0 (0.00) | 0 (0.00) |
≥ 8 | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
Risk factorsb | ||||
Elderly ≥ 65 years old | 590 (57.23) | 202 (68.71) | 340 (49.35) | 48 (100.00) |
Malignant tumor | 49 (4.75) | 27 (9.18) | 20 (2.90) | 2 (4.17) |
COPD | 53 (5.14) | 27 (9.18) | 26 (3.77) | 0 (0.00) |
Chronic kidney disease | 71 (6.89) | 46 (15.65) | 21 (3.05) | 4 (8.33) |
Type 2 diabetes mellitus | 219 (21.24) | 75 (25.51) | 139 (20.17) | 5 (10.42) |
Hypertension | 448 (43.45) | 126 (42.86) | 298 (43.25) | 24 (50.00) |
Dyslipidemia | 201 (19.50) | 52 (17.69) | 146 (21.19) | 3 (6.25) |
Immunodeficiency after solid-organ transplantation | 1 (0.10) | 1 (0.34) | 0 (0.00) | 0 (0.00) |
Obesity (BMI ≥ 30 kg/m2) | 98 (9.51) | 26 (8.84) | 72 (10.45) | 0 (0.00) |
Smoking | 252 (24.44) | 92 (31.29) | 160 (23.22) | 0 (0.00) |
Otherc | 226 (21.92) | 49 (16.67) | 157 (22.79) | 20 (41.67) |
Safety
ADR | Patients reported the event | Number of events |
---|---|---|
n (%) | ||
Total | 68 (6.60) | 78 |
Diarrhoea | 26 (2.52) | 26 |
Rash | 6 (0.58) | 6 |
Dizziness | 5 (0.48) | 5 |
Faeces soft | 4 (0.39) | 4 |
Vomiting | 3 (0.29) | 3 |
Headache | 3 (0.29) | 3 |
Nausea | 2 (0.19) | 2 |
Drug eruption | 2 (0.19) | 2 |
Urticaria | 2 (0.19) | 2 |
White blood cell count decreased | 2 (0.19) | 2 |
Hepatic enzyme increased | 2 (0.19) | 2 |
Decreased appetite | 2 (0.19) | 2 |
No. | Age/gender | Inpatient or outpatienta at the start of molnupiravir administration | COVID-19 severityb | Risk factors for severe COVID-19 illness | Vaccination against SARS-CoV-2 | Oxygen at the start of molnupiravir administration | Duration of molnupiravir administration | AE term | Cause of death | Days from the start of molnupiravir to death |
---|---|---|---|---|---|---|---|---|---|---|
1 | 90s/Female | Other | Mild | Elderly ≥ 65 years old, hypertension | Yes | 94–95% | 5 days | Asthenia | COVID-19 | 26 |
2 | 90s/Male | Other | Mild | Elderly ≥ 65 years old, others: dementia | Yes | 94–95% (oxygen administration after molnupiravir administration) | 5 days | Hypoxia | COVID-19 | 21 |
3 | 80s/Male | Other | Mild | Elderly ≥ 65 years old, type 2 diabetes mellitus | Yes | 94–95% | 4 days | Diabetic ketoacidosis | Diabetic ketoacidosis | 5 |
4 | 90s/Female | Inpatient | Mild | Elderly ≥ 65 years old | Yes | ≥ 96% | 6 daysc | Diet refusal | Senescence | 27 |
5 | Age not disclosed/male | Inpatient | Moderate II | Malignant tumor, hypertension | No | 94–95% With oxygen at start | 6 daysc | COVID-19/prostate cancer | COVID-19 | 9 |
6 | 80s/Female | Inpatient | Moderate I | Elderly ≥ 65 years old, others: chronic cardiac failure, oral administration of immunosuppressants | Yes | ≥ 96% (94–95% on the next day with oxygen) | 6 daysc | Urinary tract infection | Urinary tract infection/sepsis | 13 |
7 | 80s/Male | Other | Moderate I | Elderly ≥ 65 years old, chronic kidney disease, and high blood pressure | Yes | 94–95% | 2 days | Respiratory disorder | Unknown | 30 |
Effectiveness
Factors and variables | Total | Patients reported events | OR (95% CI) |
---|---|---|---|
n (%) | |||
Total | 612 | 16a (2.61) | – |
Gender | |||
Female | 270 | 7 (2.59) | 0.98 (0.36–2.68) |
Male (ref) | 342 | 9 (2.63) | – |
Age (years) | |||
≤ 60 | 250 | 4 (1.60) | 0.47 (0.15–1.48) |
> 60 (ref) | 361 | 12 (3.32) | – |
BMI (kg/m2) | |||
< 30 kg/m2 (ref) | 260 | 8 (3.08) | – |
≥ 30 kg/m2 | 58 | 2 (3.45) | 1.13 (0.23–5.44) |
Presence of risk factors for severe COVID-19 illness | |||
No | 20 | 0 (0.00) | < 0.01 (< 0.01 to > 999.99) |
Yes (ref) | 592 | 16 (2.70) | – |
Presence of comorbidities including risk factors for severe COVID-19 illness | |||
No | 107 | 2 (1.87) | 0.66 (0.15–2.94) |
Yes (ref) | 498 | 14 (2.81) | – |
Vaccination against SARS-CoV-2 | |||
No | 47 | 1 (2.13) | 0.85 (0.11–6.64) |
Yes (ref) | 521 | 13 (2.50) | – |
Presence of concomitant medications for COVID-19 | |||
No (ref) | 427 | 3 (0.70) | – |
Yes | 176 | 10 (5.68) | 8.51 (2.31–31.32) |