Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial

Sivapalasingam, Sumathi; Lederer, David J.; Bhore, Rafia; Hajizadeh, Negin; Criner, Gerard J.; Hosain, Romana; Mahmood, Adnan; Giannelou, Angeliki; Somersan-Karakaya, Selin; O’Brien, Meagan P.; Boyapati, Anita; Parrino, Janie; Musser, Bret J.; Labriola–Tompkins, Emily; Ramesh, Divya; Purcell, Lisa A.; Gulabani, Daya; Kampman, Wendy; Waldron, Alpana; Gong, Michelle N.; Saggar, Suraj; Sperber, Steven J.; Menon, Vidya; Stein, David; Sobieszczyk, Magdalena E.; Park, William; Aberg, Judith A.; Brown, Samuel M.; Kosmicki, Jack A.; Horowitz, Julie; Ferreira, Manuel A. R.; Baras, Aris; Kowal, Bari; DiCioccio, A. Thomas; Akinlade, Bolanle; Nivens, Michael; Braunstein, Ned; Herman, Gary; Yancopouloš, George D.; Weinreich, David M.

doi:10.1093/cid/ciac153

Cited by 27 publications

(18 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Safety outcomes in some RCTs have shown that sarilumabtreated patients had more secondary respiratory bacterial infections, respiratory failure, and neutropenia (García-Vicuña et al, 2022). Another RCT evaluating the safety profile of sarilumab in COVID-19 patients reported that more patients in the treatment arm had elevations in liver function tests compared to the placebo group (Sivapalasingam et al, 2022). Similar studies have reported an increased incidence in the number of serious bacterial and fungal infections (Hermine et al, 2021).…”

Section: Safetymentioning

confidence: 89%

“…Its use is approved for treating rheumatoid arthritis, but it has been evaluated as a potential treatment for COVID-19. The efficacy of sarilumab in COVID-19 is controversial: some RCTs show better outcomes with early IL-6 blockade through a single dose of sarilumab (Merchante et al, 2022), while others have failed to show significant improvements in clinical status or mortality (Sivapalasingam et al, 2022). However, sarilumab is recommended by some guidelines as an alternative to tocilizumab in the treatment of COVID-19 (Nih, 2022).…”

Section: Sarilumabmentioning

confidence: 99%

See 1 more Smart Citation

Immune-related adverse events of biological immunotherapies used in COVID-19

et al. 2022

View full text Add to dashboard Cite

The use of biological immunotherapeutic drugs is one of the options currently being evaluated and employed to manage COVID-19, specifically monoclonal antibodies, which have shown benefit by regulating the excessive immune response seen in patients with severe infection, known as a cytokine storm. Tocilizumab has received particular importance for this clinical application, as has sarilumab. Both drugs share a substantial similarity in terms of pharmacodynamics, being inhibitors of the interleukin six receptor (IL-6Rα). Furthermore, sotrovimab, a neutralizing anti-SARS CoV-2 antibody, has gained the attention of the scientific community since it has recently been authorized under certain circumstances, positioning itself as a new therapeutic alternative in development. However, despite their clinical benefit, biological immunotherapies have the potential to generate life-threatening immune-related adverse events. Therefore it is essential to review their incidence, mechanism, and risk factors. This review aims to provide a comprehensive understanding of the safety of the biological immunotherapeutic drugs currently recommended for the treatment of COVID-19, provide a review of the known immune-mediated adverse events and explore the potential immune-related mechanisms of other adverse reactions.

show abstract

Section: Safetymentioning

confidence: 89%

Section: Sarilumabmentioning

confidence: 99%

Immune-related adverse events of biological immunotherapies used in COVID-19

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The remaining 18 trials contained at least one eligible patient and are included in this network meta-analysis. 14 trials are published [4,[18][19][20][21][22][23][24][25][26][27][28], one is reported on a pre-print server [29] and three are not yet published (see Table 1 for trial registration numbers). These 18 trials had compared tocilizumab (13 trials) or sarilumab (4 trials) or both (1 trial) with usual care or placebo and include 3710 patients (40%; 1278 deaths by 28 days) who received corticosteroids and either non-invasive or mechanical ventilation and were therefore eligible for inclusion in the network meta-analysis (Fig 1).…”

Section: Study Selection and Description Of Eligible Trialsmentioning

confidence: 99%

Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis

et al. 2022

View full text Add to dashboard Cite

Background A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. Methods Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. Findings One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71–0·95, p = 0·008]] and sarilumab [0·80 [0·61–1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81–1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. Conclusions Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.

show abstract

“…Subsequently, three immunomodulators have been reported to reduce mortality risk in patients who require supplemental oxygen, and the Taskforce conditionally recommends their use in these patients. Tocilizumab (eleven studies, 7221 participants [21][22][23][24][25][26][27][28][29][30][31] ) and sarilumab (seven studies, 3668 participants [32][33][34][35][36][37][38] ), are monoclonal antibodies against the interleukin-6 receptor; baricitinib (four studies, 10 815 participants [39][40][41][42] ) is a Janus kinase (JAK) inhibitor.…”

Section: Adults Who Require Supplemental Oxygenmentioning

confidence: 99%

Care for adults with COVID ‐19: living guidelines from the National COVID ‐19 Clinical Evidence Taskforce

White

McDonald

Barber

et al. 2022

Medical Journal of Australia

View full text Add to dashboard Cite

Introduction:The Australian National COVID-19 Clinical Evidence Taskforce was established in March 2020 to maintain up-to-date recommendations for the treatment of people with coronavirus disease 2019 . The original guideline (April 2020) has been continuously updated and expanded from nine to 176 recommendations, facilitated by the rapid identification, appraisal, and analysis of clinical trial findings and subsequent review by expert panels.1 Drug treatments recommended for use in people with severe or critical coronavirus disease 2019 (COVID-19) (ie, who require supplemental oxygen) * Drug treatment Category RecommendationCorticosteroids (systemic) Recommended Use intravenous or oral dexamethasone for up to ten days (or another acceptable regimen) in adults who require supplemental oxygen (including mechanically ventilated patients). Conditional recommendation againstDo not routinely use dexamethasone (or other systemic corticosteroid) to treat COVID-19 in adults who do not require supplemental oxygen. Remdesivir Conditional recommendationConsider using remdesivir in adults who require supplemental oxygen but not non-invasive or invasive ventilation. Not recommendedDo not use remdesivir in adults hospitalised with COVID-19 who require non-invasive or invasive ventilation. Tocilizumab Conditional recommendationConsider using tocilizumab in adults who require supplemental oxygen, particularly when there is evidence of systemic inflammation. Sarilumab Conditional recommendationConsider using sarilumab in adults who require high-flow oxygen, non-invasive ventilation, or invasive mechanical ventilation. BaricitinibConditional recommendation Consider using baricitinib in adults hospitalised with COVID-19 who require supplemental oxygen. Casirivimab/imdevimab Conditional recommendation Consider using casirivimab/imdevimab in SARS-CoV-2 antibodyseronegative adults hospitalised with moderate to critical COVID-19. Not recommended Do not use casirivimab/imdevimab in SARS-CoV-2 antibodyseropositive adults hospitalised with moderate to critical COVID-19. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. * Status: 1 August 2022. For full recommendations, see Supporting Information, table 2. ◆

show abstract

Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial

Cited by 27 publications

References 18 publications

Immune-related adverse events of biological immunotherapies used in COVID-19

Immune-related adverse events of biological immunotherapies used in COVID-19

Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis

Care for adults with COVID ‐19: living guidelines from the National COVID ‐19 Clinical Evidence Taskforce

Contact Info

Product

Resources

About