key: cord-0842998-qqg80f52
authors: Chochoł-Labun, Joanna; Wachnicka-Truty, Renata; Sinica-Latecka, Małgorzata; Sikorska, Katarzyna; Koziński, Marek
title: Successful treatment of severe COVID-19 pneumonia with tocilizumab: A series of three cases
date: 2021-10-27
journal: Cardiol J
DOI: 10.5603/cj.a2021.0138
sha: 49ab92a609b3ac24b72b4bb3b44773c07fc0c707
doc_id: 842998
cord_uid: qqg80f52

nan

Severe coronavirus disease 2019 (COVID-19) pneumonia associated with cytokine storm remains a challenge for clinicians. It is usually complicated by multiple organ dysfunction and despite optimal contemporary therapy leads to high mortality.

In this research letter, we present 3 consecutive patients with severe COVID-19 pneumonia who between January and March 2021 were successfully treated with tocilizumab (a humanized antibody to the soluble interleukin-6 [IL-6] receptor) added to the standard therapy. This treatment was approved by the local ethics committee and subsequently all patients provided an informed written consent. On admission, all patients were moderately/severely ill with predominant respiratory failure and markedly elevated C-reactive protein (CRP) concentration (Table 1) . Therapy with tocilizumab was initiated on day 1 in 2 patients and on day 6 in the 3 rd one when he developed respiratory collapse requiring high flow oxygen therapy. All patients received two doses of tocilizumab and then their CRP concentration dropped on average by 71%. Following administration of tocilizumab combined with best known therapy, all patients were slowly and continuously improving. They all were discharged home in a relatively good condition and at a short-term follow-up are mildly symptomatic or asymptomatic.

The decision to use tocilizumab was based on the promising results of randomized clinical trials (RCTs) published since March 2020 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] . The largest and most recent study with the most spectacular outcomes is the RECOVERY trial [1] . When we treated our patients its results have only been published as a preprint. This trial included 4,116 participants receiving invasive ventilation (14%), non-invasive ventilation (41%) or usual oxygen therapy (45%). All enrolled patients had oxygen saturation < 92% and CRP concentration > 75 mg/dL. Median CRP in the RECOVERY trial was 143 [interquartile range 107-204] mg/L which is similar to our patients. Additionally, 82% of patients in the REVOVERY trial received systemic corticosteroids at randomization. The primary endpoint (all-cause 28-day mortality) was substantially reduced in the tocilizumab on top of standard care vs. standard care alone group (29% vs. 33%, p = 0.007), with consistent results in all predefined subgroups. Significant reductions in terms of secondary endpoints were also achieved in tocilizumab-treated patients (discharge from hospital alive within 28 days [54% vs. 47%], composite outcome of invasive mechanical ventilation or death [33% vs. 38%] and use of hemodialysis or hemofiltration [5% vs 7%]). Tocilizumab benefits were observed regardless of the level of respiratory support and were additional to the benefits of systemic corticosteroids, another class of anti-inflammatory agents. Also, the results of two moderate size RCTs indicated clinical benefits of tocilizumab. In the REMAP-CAP trial conducted in critically ill patients with COVID-19 pneumonia receiving organ support in Table 1 . Characteristics of patients with severe COVID-19 pneumonia and respiratory failure treated with tocilizumab. [2] . Similarly, the EMPACTA trial demonstrated superiority of tocilizumab (n = 249) over placebo (n = 128) on the primary composite endpoint of mechanical ventilation or death by day 28, but without any improvement in mortality [3] . This study included only patients who did not require mechanical ventilation at randomization. Importantly, several small/moderate size (all largely underpowered for assessment of hard clinical endpoints) RCTs indicated a neutral effect of tocilizumab on clinical outcomes [4] [5] [6] [7] , with some minor benefits seen in the CORIMUNO-19 study [5] . On the other hand, the TOCIBRAS trial was stopped early after inclusion of 129 participants due to a signal of increased mortality at 15 days related to tocilizumab therapy (11/65 [17%] vs. 2/64 [3%]) [8] . This finding may be simply due to chance, considering the very low mortality in the standard care alone group. In all of the RCTs discussed above, adverse events were not more frequent in the tocilizumab vs. placebo/standard care group [1] [2] [3] [4] [5] [6] [7] [8] . Finally, an updated meta-analysis of all available RCTs performed by the ROCOVERY investigators shows all-cause mortality benefit in patients hospitalized for COVID-19 pneumonia and treated with tocilizumab added to usual care when compared with the usual care alone group (relative risk 0.87; 95% confidence interval 0.79-0.96; p = 0.005), with a substantial heterogeneity among the included trials [1] . Furthermore, it is suggested that tocilizumab may exert an additive beneficial effect in remdesivir-treated patients [9] , as was used in the present case series. Based on the totality of the research evidence [10] and our clinical experience, we believe that tocilizumab is well tolerated and may be beneficial on top of standard therapy if early initiated in patients with COVID-19 pneumonia and both enhanced inflammatory response and a large extent of the involved lung tissue. However, further RCTs are necessary to define best tocilizumab responders. The need of temporary low flow oxygen supplementation at home *No control CT was performed after deterioration of the respiratory status as the patients was treated with high flow oxygen therapy and we were not able to transport him safely without tracheal intubation; CRP -C-reactive protein; CT -computed tomography; KDIGO -Kidney Disease: Improving Outcomes; pO2 -partial pressure of oxygen; SpO2 -oxygen saturation www.cardiologyjournal.org

Tocilizumab in patients admitted to hospital with COV-ID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Interleukin-6 receptor antagonists in critically ill patients with Covid-19

Tocilizumab in patients hospitalized with Covid-19 pneumonia

Efficacy of tocilizumab in patients hospitalized with Covid-19

Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial

Tocilizumab in hospitalized patients with severe Covid-19 pneumonia

Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial

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Interleukin-6 blocking agents for treating COVID-19: a living systematic review