Review
Copyright ©The Author(s) 2022.
World J Virol. May 25, 2022; 11(3): 113-128
Published online May 25, 2022. doi: 10.5501/wjv.v11.i3.113
Table 2 List of recent clinical trials and observational studies regarding interleukin-6 blocker monoclonal antibodies in severe acute respiratory syndrome coronavirus 2
Study design
Inclusion criteria
Interventions
Number of patients
Results
Ref.
Observational retrospectiveSevere SARS-CoV-2 positive ICU admitted patients, with or without respiratory failureSingle 400 mg TCZ dose, without antimicrobialprophylaxis55 severe patients were treated,Compared with 41 untreated (non-severe) patientsLower mortality rate among treated patients against more disease severity, with no serious side effects and no significantly different increased infection rates[53]
Quasi-experimentalSARS-CoV-2 positive patients with respiratory failure or a need for supplemental oxygen, with clinical or laboratory signs of acute inflammationComparing CSs, and TCZ (8 mg/kg up to 800 mg/dose up to 3 doses)33 patients in the TCZ group and 60 in the CS group.These drugs both reduced the need for supplemental oxygen and ICU stay to the same level, but in the CS group the survival rate was higher, use of TCZ was safe[100]
CohortCOVID-19 patients with respiratory failure and acute inflammatory laboratory findings, such as an elevated CRP levelAnakinra: 5 mg/kg BD until clinical improvement; TCZ: 400 mg single dose, repeated according to the clinical condition; Sarilumab: 400 mg single dose62 patients received IL-1 blocker and 55 IL-6 blocker (26 sarilumab and 29 TCZ) (severe patients); 275 without IL blockade (standard of care only)IL-6 blockade had only limited effectiveness in individuals with high concentrations of CRP, but IL-1 blockade reduced the mortality rate in all patients[50]
Retrospective observationalSevere patientsTocilizumab use was compared with standard of care in ICU patients78 severe patients received tocilizumab and were compared with 112 severe patients who received standard of carePatients on tocilizumab had a longer hospital and ICU stay and more costs with no reduction in the mortality rate[101]
Retrospective observationalSevere SARS-CoV-2 patients with respiratory failureTCZ 8 mg/kg30 severe patients with respiratory failure who received TCZ were evaluated for inflammatory markers and clinical condition after treatmentPatients had better oxygenation and inflammatory markers decreased after treatment with TCZ[102]
Randomized, double-blindclinical trialHospitalized patients without respiratory failure and mechanical ventilation, but with decreased SpO2 in room air 8 mg/kg up to 800 mg, TCZ; One-two doses249 TCZ; 128 SOCLikelihood ratio of; serious adverse outcomes were significantly lower in the treatment group; But no reduction in all-cause mortality rate[8]
Clinical trialModerate and severe patients according to the clinical status, with higher IL-6 levels, neither ICU admitted nor on mechanical ventilationTCZ 400 mg; Single-dose29 patients were treated with TCZ and 32 received standard of care onlyTCZ was safe but did not show any significant difference in clinical improvement[103]
Cross-sectional, observationalSevere patients with high levels of inflammatory markersTCZ 4 mg/kg54 patients were treated with TCZSignificant reduction in neutrophil count and CRP[104]
Clinical trialPatients with hyper-inflammatory state and acute respiratory failureTCZ 8 mg/kg (up to 800 mg); After 12 h: second dosage66 severe patients received TCZ and were compared with 60 patients who received standard of careNot effective in decreasing the risk of disease deterioration[105]
Open-label clinical trialProven SARS-CoV-2 infection, with the need for respiratory support and recent worsening in the clinical conditionTCZ 8 mg/kg46 moderate and severe patients were treated with TCZTreatment improved respiratory function[48]
Clinical trialHigh levels of IL-6Moderate and severe disease severityTCZ 400 mg (second dosage after 24h)34 patients were treated and 31 were notTreatment with TCZ improved respiratory condition without reducing the mortality rate[106]
Clinical trialSevere and critical patientsSarilumab 400 mgTotal = 416 (Sarilumab 400 mg, n = 173; Placebo, n = 84; Sarilumab 200 mg, n = 159); Primary analysis between 194 severely ill patients who needed respiratory supportDid not meet the primary and secondary endpoints in improving disease progression and the study stopped further recruitmentNCT04315298 [107,108]
Randomized, double-blindclinical trialSevere patients with decreased SpO2 without supplemental oxygenTCZ 8 mg/kg up to 800 mg2:1 Placebo+ Standard of care (151); TCZ+ SOC (301)No significant benefits on mortality rate or clinical improvement, but a positive effect on hospitalization duration was observed with no significant side effects compared with the control groupNCT04320615 [109]
Retrospective cohortSARS-CoV-2 positive patients with severe pneumoniaTCZ one to two doses, 400–800 mg every 12 hn = 62 treated, n = 86 untreatedTreated patients showed significantly lower leukocytosis compared to the control group after 14 d. D-dimer and ferritin initially increased and then decreased in the treated group. The mortality rate at 28 d was statistically lower in the TCZ group. A longer hospital stay was shown in these patients although this was not statistically significant. Ten patients developed an infection during hospitalization[62]
Retrospective cohortModerate to severe SARS-CoV-2 patientsOne to two doses of TCZ 8 mg/kg170 treated; 655 untreatedClinical improvement was significantly better in the treatment group compared with the control group. A significant reduction in the mortality rate at 21 and 28 d was found in patients with respiratory failure and patients with IL-6 levels above 100 pg/mL[110]
Randomized clinical trialCritical patients with respiratory failure who were admitted to the ICU TCZ one to two doses (8 mg/kg); Sarilumab (a single dose of 400 mg); Other interventions: Anakinra and interferon beta-1a350 on TCZ; 45 on sarilumab; 1136 on another immunomodulator; 397 on no immunomodulationIL-6 blocking agents were effective in reducing the mortality rate. When added to corticosteroids, this effect was stronger compared with IL-6 blockade aloneNCT02735707 [74]
Randomized, controlled, open-label clinical trialCOVID-19 patients with worsening clinical status or with high CRP levels after 21 d of the first randomization to dexamethasone, lopinavir–ritonavir, hydroxychloroquine, azithromycin, or colchicine or convalescent plasma or a combination of two anti-SARS-CoV-2 spike protein antibodies (REGN-COV2) or aspirinA single dose of TCZ according to the patient’s weight2022 received TCZ; 2094 received standard of careTCZ group had a significantly lower mortality rate, need for mechanical ventilation, and higher chance of hospital discharge at day 28. This effect was similar in patients randomized less than or more than two days from hospitalization. In patients who were on mechanical ventilation at the time of drug administration, this drug had no significant effect on improving prognosis[67]
Randomized, double-blindclinical trialSevere COVID-19 patientsSarilumab 200 or 400 mg, single dosen = 153 sarilumab 400 mg, n = 141 sarilumab 200 mg, n = 75 placeboNo significant effectiveness was found in the treatment groups compared with the control group[111]
Randomized, double-Blind, placebo-controlled trialPatients with COVID-19 in a hyper-inflammatory stateTCZ 8 mg/kg up to 800 mgTCZ (n = 161); Placebo (n = 81) + standard of careNo significant benefits from early TCZ administration in COVID-19 were observed[112]