Systematic Reviews
Copyright ©The Author(s) 2021.
World J Methodol. May 20, 2021; 11(3): 95-109
Published online May 20, 2021. doi: 10.5662/wjm.v11.i3.95
Table 1 Baseline characteristics of tocilizumab treated patients
Ref.
Country
Type of study
No. of pts
Median follow up (d)
Male/Female, %
Median age (yr)
CV Comorbities, %
Respiratory/diabetes %
Other/cancer, %
Other medications, %
Ventilatory status (Baseline to end of follow up, %)
ICU admission %/time to ICU admission (d)
Alattar et al[11], 2020QuatarRetrospective2514 92/85812 HTN-/48CKD 16/4HCQ (100), AZITRO (96), lopinavir/ritonavir (96), ribavirin (88), and INF 1-α2a (60)56 (invasive)100/1
Alberici et al[12], 2020ItalyRetrospective 64 ----/--/-Steroids, antivirals, HCQ33 (16 worsened)-/-
Capra et al[13], 2020ItalyRetrospective (with ctr arm1)82 (n = 62 TCZ)9 73/276363 HTN-/16-/-HCQ (100), lopinavir/ritonavir (100)35.2 (27% worsened)4.8/-
Colaneri et al[14], 2020ItalyRetrospective with prop. score112 (n = 21 TCZ)7 90/1062.347.6 HTN0/9.519/4.7HCQ, AZITRO, steroids (100)-14/-
Hassoun et al[15], 2020United StatesRetrospective9-66/336055 HTN11/1166/-HCQ, AZITRO (100) steroids (33), antibiotics (66)-89/-
Klopfenstein et al[16], 2020FranceCase control45 (n = 20 TCZ)--76.855 HTN/70 CVS disease20/25-/35HCQ or lopinavir/ritonavir + antibiotics ± steroids (100) -0/-
Luo et al[17], 2020ChinaRetrospctive15-80/207366 HTN-/26.6-/-Steroids (53)6.6 (33.3% worsened)-/-
Quartuccio et al[18], 2020ItalyRetrospective (with ctr arm1)111 (n = 42 TCZ)17.8 78.6/21.462.447.6 HTN-/--/-Antivirals (100), HCq (92.9) steroids (40); antibiotics (28.6)65 (invasive)57/-
Sciascia et al[19], 2020ItalyProspective63-89/1162.6454.7/9.5-Lopinavir/ritonavir (71), darunavir/cobicistat (29)957.9/-
Toniati et al[20], 2020ItalyProspective10010 88/1262629/1711/6HCQ, lopinavir/ritonavir or remdesivir, antibiotic, steroids69 (n = 23 worsened)43/-
Xu et al[21], 2019ChinaRetrospective21-86/1456.857.29.6/23.8CKD 4.8/-Lopinavir/ritonavir, IFN-α, ribavirin, steroids (100)100-/-
Ramaswamy et al[22], 2020United StatesCase control86 (n = 21 TCZ)-61.9/38.163.214.3 HTN/heart disease, AF or stroke 19.128.6/14.3-/0HCQ (81), AZITRO (23.8), steroids (42.9)-47.6/-
Rimland et al[23], 2020United StatesRetrospective1117 82/185973 HTN/18 CVS27/36Renal or liver 18/9HCQ (36), AZITRO (64)54 (10% worsened)73/-
Sanchez-Montalva et al[24], 2020Spain Prospective 82-63/3759.139 HTN/6.1 heart failure/12.2 AF23.5/19.5Liver 1.2/-HCQ (98.9), lopinavir/ritonavir (76.8), AZITRO (96.3), darunavir/cobicistat (25)53 (52% worsened)2.9/-
Wadud et al[25], 2020United StatesCase control94 (n = 44 TCZ)--/-55.5--/--/----
Campochiaro et al[26], 2020ItalyRetrospective65 (n = 32 TCZ)28 91/96437 HTN/12 CAD3/12CKD 9/6HCQ, AZITRO, lopinavir/ritonavir (100)910/-
Morena et al[27], 2020ItalyProspective 5130 78.4/21.66029.4 HTN/49 CVS disease9.8/11.85.9/5.9HCQ (98), antibiotics (76), lopinavir/ritonavir (82), remdesivir (42)66.6 (33% worsened)11.8/-
Kimmig et al[28], 2020United StatesRetrospective (with ctr arm)60 (n = 28 TCZ)-46.8/53.263.853.6 HTN/43 other35.7/14.314/14.3---
Roumier et al[29], 2020FranceCompassionate use59 (n = 30 TCZ)8 80/205020 HTN/13 CVS13/2333/-HCQ (6.6), steroids (6.6)-23.3/-
Ip et al[30], 2020United StatesRetrospective547 (n = 134 TCZ)30 78/226271.6 HTN and coronary arthery disease15/3515/9HCQ + AZITRO (92), steroids (66)-100/-
Perrone et al[31], 2020ItalyPhase 2 and expansion cohort1221 (n = 708 TCZ3)30 82/1861% > 6068 heart disease or HTN-/15-/-HCQ (75), anti-retroviral (65), antibiotics (50), steroids (28)-16 invasive ventilation/-
Perez-Tanoira et al[32], 2020SpainCohort study562 (n = 36 TCZ)--/----/--/----
Somers et al[33], 2020United StatesObservational 154 (n = 78 TCZ)47 68/325585 HTN or heart failure54/13CKD 35/-HCQ (26), steroids (29), remdesivir (3)56 (18 and worsened)100/41 < 24 h, 36 > 48 h
Heili-Frades et al[34], 2020SpainCohort study4712 (n = 366 TCZ)2--/----/--/---40.7/-
Issa et al[35], 2020France Retrospective10-100/06660 HTN-/30-/-HCQ (100), steroids (30)5070/7 d
Garcia et al[36], 2020SpainRetrospective 171 (n = 77 TCZ)-58.8/51.261.561 HTN or heart disease10.3/15.6-/-Antivirals (100, steroids (50)9010.3/-
Ayerbe et al[37], 2020United KingdomRetrospective2075 (n = 421 TCZ)8 -/----/--/----/-
Borku Uysal et al[38], 2020TurkeyRetrospective 1222 50/5065.858 HTN16/58CKD 8/16HCQ and antivirals (100), AZITRO (50), antibiotics (58)8217/-
Fernandez-Cruz et al[39], 2020SpainRetrospective463 (n = 189 TCZ)--/----/--/-Steroids (100), other not available--/-
Garibaldi et al[40], 2020United StatesCohort study832 (n = 39 TCZ)--/----/--/----/-
Martínez-Sanz et al[41], 2020SpainCohort study1229 (n = 260 TCZ)-73/276517 HTN, 8 CAD, 2 heart failure 18/15CKD 4/---19/6 d
Petrak et al[42], 2020United StatesRetrospective145-64/3658.1---Corticosteroids (60), HCQ + AZITRO (98.6)--/-
Rossi et al[43], 2020FranceCase control246 (n = 106 TCZ)2866/346460 HTN, 23.6 CVS16/45-/5.7Antibiotics (100), HCQ (83), steroids (40), lopinavir/ritonavir (0.9)--/-
1Control arm consisted in patients treated with hydroxycloroquine + lopinavir/ritonavir before tocilizumab availability.
2Hospitalized cohort only.
3Modified intent to treat analysis. CVS: Cardiovascular disease; CAD: Coronary arthery disease; AF: Atrial fibrillation; HTN: Hypertension; CKD: Chronic kidney disease; pts: Patients; HCQ: Hydroxycloroquine; AZITRO: Azitromycin; -: Not availble; TCZ: Tocilizumab; ICU: Intensive care unit.
Table 2 Laboratory and radiological characteristics of patients treated with tocilizumab
Ref.
Fever (baseline) °C/%
O2 sat. %
Cough %
Dyspnea %
Leucocytes 109/L
Lymphocites/Neutrophil 109/L
PLT 109/L
Hb g/dL
LDH
Liver tests IU/L
CRP mg/L
PCT ng/L
D-dimer
IL6 ng/L
Imaging %
Alattar et al[11], 202038/92-84726.00.9/5.0208--46/3095.20.38 --Infiltrates and ground glass opacities 100
Alberici et al[12], 2020-/------/----------
Capra et al[13], 202038/------/-----1230.6--Bilateral pulmonary opacities 100
Colaneri et al[14], 2020-/-----0.6/8.4303-44538/7221.30.24--Interstitial lung disease 100
Hassoun et al[15], 2020-/------/-----/------
Klopfenstein et al[16], 2020-/-90---0.67/-----/-158---≥ 50% lung involvement 60
Luo et al[17], 2020-/------/-----/-96--71-
Quartuccio et al[18], 2020-/----55400.68/4.5157-625-/-79.05-83563.5-
Sciascia et al[19], 2020< 38/39.7-------------Bilateral pulmonary infiltrates
Toniati et al[20], 2020> 37.5/85-557360.7817713.641355/3997-52541 Ground glass opacities and consolidation, bilateral pulmonary infiltration
Xu et al[21], 2019-/100-66.7-6.30.97170-37031/29750.330.8153Ground glass opacities and focal consolidation, peripheral and subpleural
Ramaswamy et al[22], 2020-/-----1.1/6.7200--60/43.515.92.22900371-
Rimland et al[23], 2020-/----8.5-/0.8230-120351/35197.3-343.530.65-
Sanchez-Montalva et al[24], 202037.7/91.59486.665.99.20.86/19913.344653/4117.98-29574.8-
Wadud et al[25], 2020---------------
Campochiaro et al[26], 202037.6/------/---469-/-156----
Morena et al[27], 202074.5/--62.754.99.10.8/7.3230-47048/39189-1706116Bilateral pulmonary opacities 100
Kimmig et al[28], 2020---------------
Roumier et al[29], 2020----------189-3712--
Ip et al[30], 202080-7880--/-----/-----
Perrone et al[31], 2020-/------/-----/-30----
Perez-Tanoira et al[32], 2020-/------/-----/------
Somers et al[33], 2020-/----12.10.9/---62750/76185-2400--
Heili-Frades et al[34], 2020-/------/-----/------
Issa et al[35], 2020-/100-----/-----/-246-1354-Ground glass opacities
Garcia et al[36], 2020-/98.7-8343-0.87/-----/-97-918--
Ayerbe et al[37], 2020-/------/-----/------
Borku Uysal et al[38], 2020-/9292100676.11.09/4.318013.825933/3954-599-Ground glass opacities
Fernandez-Cruz et al[39], 2020-/------/-----/------
Garibaldi et al[40], 2020-/------/-----/------
Martínez-Sanz et al[41], 202036.8/-91---0.89/5.4--669-/32113-80970-
Petrak et al[42], 2020--------538-53.3-1.3--
Rossi et al[43], 202037.5/-94---1.128/-----168----
-: Not available; PLT: Platelets; Hb: Hemoglobin; CRP: C reactive protein; PCT: Procalcitonin C; IL-6: Interleukin-6; sat: Saturation; LDH: Lactate dehydrogenase.
Table 3 outcome of patients treated with tocilizumab therapy
Ref.
N° TCZ administered (median doses)
Death %
Dismissed %
Median hospitalization (d)
TCZ AEs %
Comparison with other medications or no TCZ
NOS Scale
ROBIN risk
Alattar et al[11], 20201 1236 (from ICU)-Anemia 64; ALT ↑ 44 HR for discharge from ICU 0.64 (0.37-1.11)8Low
Alberici et al[12], 202013316 ---6Moderate
Capra et al[13], 20201 89212.5-OR for OS 0.036 (0.07-0.18)°7Low
Colaneri et al[14], 20202 23.885.7 (from ICU)20OR for OS 0.78 (0.06-9.34); OR for ICU 0.11 (0-3.38)7Low
Hassoun et al[15], 20201225513.5 (n = 7)--5Low
Klopfenstein et al[16], 20201 or 2255513-OR for OS and ICU admission 0.36 (0.1-1.3) and 0.03 (0.002-0.56); OR for mechanical vent 0.05 (0.003-0.93)5Low
Luo et al[17], 2020120----5High
Quartuccio et al[18], 202019.528.5--OR for OS 14.5 (0.76-278.3); OR for ICU admission 220.9 (12.7-3826.1) 8Moderate
Sciascia et al[19], 20201 (2 in 82.5%) 11----6Moderate
Toniati et al[20], 20201 (2 in 87%)2015-Septic shock (n = 2), GI perforation (n = 1)-8Low
Xu et al[21], 20191 (2 in 14.3%)010015.1--5Moderate
Ramaswamy et al[22], 20201 (2 in 38%)14.3---HR for OS 0.25 (0.07-0.9) 5Moderate
Rimland et al[23], 20201 271818--7Low
Sanchez-Montalva et al[24], 2020126.841.5---6Low
Wadud et al[25], 2020-38.6---OR for OS 0.58 (0.25-1.32)6Moderate
Campochiaro et al[26], 20201 (2 in 28%)156313.5SAEs (25)OR for OS 0.38 (0.11-1.27); OR for ICU admission 0.33 (0.13-8.5)8Low
Morena et al[27], 2020-2761-AST/ALT ↑ 29, PLT 14, neutropenia 6, rash 2-8Low
Kimmig et al[28], 20201 (2 in 10.7%)42.925-Infections 71.4OR for OS 2.25 (0.75-2.24)6Moderate
Roumier et al[29], 202011020--OR for OS 0.25 (0.05-1.03); OR for ICU 0.17 (0.06-0.48)7Low
Ip et al[30], 20201 (78%)46--Bacteriemia (13), secondary pneumonia (9)OR for OS 0.66 (045-0.99) 8Low
Perrone et al[31], 20201 (59.8), 2 (54.5)20--26.4 G3-5; 14.4 G1-2OR for 30-d OS 0.7 (0.41-1.22) and 1.22 (0.86-1.92) in phase 2 and validation cohort8Low
Perez-Tanoira et al[32], 2020-27.7---OR for OS 1.015 (0.47-2.18)5Moderate
Somers et al[33], 20201185620.4Superinfection (54)OR 0.39 (0.18-0.82) 8Low
Heili-Frades et al[34], 2020-22.4----6Moderate
Issa et al[35], 2020110-11 (ICU)--5High
Moreno-Garcia et al[36], 2020-10.384.4--OR for ICU 0.3 (0.12-0.71) and OR for OS 0.52 (0.21-1.29) 5Moderate
Ayerbe et al[37], 2020-21.1---OR for OS 1.9 (1.44-2.51)5High
Borku Uysal et al[38], 202020100---6Moderate
Fernandez-Cruz et al[39], 2020-----OR for OS 0.69 (0.41-1.19)5High
Garibaldi et al[40], 2020-5---OR for OS 1.14 (0.46-2.81)5Moderate
Martínez-Sanz et al[41], 2020123-13-OR for OS 2.19 (1.54-3.1) 5Low
Petrak et al[42], 20201 (84.8), 2 (15.2)28.348.3---5Moderate
Rossi et al[43], 2020128.9---HR for OS 0.29 (0.17-0.49) 8Low
-: Not availble; NOS: Nottingham-ottawa-scale; ROBIN: Risk of bias of non-randomized studies; ALT: Alanine aminotransferase.