biostudies-literature00520Stone JHGenentechNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHS2333-2344https://www.ebi.ac.uk/biostudies/studies/S-EPMC7646626biostudies-literatureUnknown383(24)<h4>Background</h4>The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.<h4>Methods</h4>We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses.<h4>Results</h4>We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo.<h4>Conclusions</h4>Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).The New England journal of medicineEfficacy of Tocilizumab in Patients Hospitalized with Covid-19.PMC7646626ML42488K08 DK114563P30 AI042853T32 HL094301K23 HL154863T32 AI007387Collier DPatel AStone JHFreiman JMShah RWallwork RSerling-Boyd NJNorth CMSacks CBolster MBGavralidis AHalvorsen YDRutherford HSchrager HChan SMatza MAFernandes ADScherer AOomen VAsundi ABombard JD'Silva KMShinnick DDougan MThurber THuckins DSAxelrod MLin NKim ALee PLockwood MMKohler MJami HKim JYinh JMThurber TKMallada JWoolley AEDau JYinh JGanatra SSagar MCheng VMughal UKivett DRoche SMckenney KDagher ZNader CGerbands JLaCamera PSerling-Boyd NAnsari SUnizony SHSchoenfeld SSusan ALiokos AD'Silva KBACC Bay Tocilizumab Trial InvestigatorsBrownmiller SBowman KSchmidt APerugino CAHealy BCBensaci AMLockwood MOganezova KDrobni ZDHuerta JChen YNikiforrow SHuckins DBasciota MUnizony SYang NTedrow JNikiforow SWoolley AFleisher JSen PHorick NKPerugino CWeber BNCubbison CFernandes AHarvey LMatza MMeyerowitz ECoraini AMyers JKim AYFoulkes ASNeilan TGGilman HNorth CFrigault MJMansour MFrigault MSacks CAStone JPincus MDBasein TCollier DSBowman KADwyer MZinchuk KZafar AWallwork RSHarrison LHartmann SChang YTMoraco ACubbinson CNeilan TVerma VMansour MKBolster MDrobni ZWeber BMlynarczyk CPincus MKhambhati J52falseEfficacy of Tocilizumab in Patients Hospitalized with Covid-19.<h4>Background</h4>The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.<h4>Methods</h4>We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses.<h4>Results</h4>We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo.<h4>Conclusions</h4>Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).2020-01-01T00:00:00Z2020 Dec2024-11-20T11:37:18.079Z2020-11-22T09:39:53ZS-EPMC76466263308585710.1056/NEJMoa2028836