Risk of reactivation of hepatitis B virus (HBV) and tuberculosis (TB) and complications of hepatitis C virus (HCV) following Tocilizumab therapy: A systematic review to inform risk assessment in the COVID era

Campbell, Cori; Andersson, Monique; Ansari, Azim; Moswela, Olivia; Misbah, Siraj; Klenerman, Paul; Matthews, Philippa C.

doi:10.1101/2021.03.22.21254128

Cited by 6 publications

(7 citation statements)

References 34 publications

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“…After evaluating the other 92 articles for eligibility, 42 were excluded for the following reasons: one study investigated tocilizumab combined with another IL‐6 inhibitor, 20 two discussed therapies other than tocilizumab, 21,22 37 were not systematic reviews, 23–59 and two were systematic reviews of preclinical or animal studies 60,61 . Finally, 50 articles met the eligibility criteria and were included in the present umbrella review 6,28,62–109 (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Tolzali

Noori

Shokri

et al. 2022

Reviews in Medical Virology

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Tocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 10 9 /L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID‐19.

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Section: Resultsmentioning

confidence: 99%

Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Tolzali

Noori

Shokri

et al. 2022

Reviews in Medical Virology

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“…In COVID patients treated with steroids, therapeutic immunosuppression can lead to the reactivation of LTB. In addition, FDA-approved monoclonal antibodies like tocilizumab, bamlanivimab, and estesevimab for the treatment of COVID-19 in early stages can directly cause re-activation of TB [ 14 - 16 ].…”

Section: Discussionmentioning

confidence: 99%

Reactivation of Tuberculosis in the Setting of COVID-19 Infection

Noori¹,

Younes²,

Latif³

et al. 2022

Cureus

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) was declared a pandemic by WHO in March 2020. The causative organism has since undergone a series of mutations. COVID-19 primarily being a respiratory illness causes pre-existing pulmonary diseases to show worse clinical outcomes. About one-third of the world’s population is thought to be infected with latent Mycobacterium tuberculosis (MTB). Both previous and newly developed tuberculosis (TB) infection are risk factors for COVID-19 and are associated with poor outcomes. T lymphocytes play a pivotal role in defense against MTB and with evidence suggesting depletion of T lymphocytes in COVID-19, it can be postulated that COVID-19 can increase the risk of reactivation of latent TB. Given that a large population around the globe is infected with latent tuberculosis, it is interesting to study and note cases where the virus leads to the reactivation of latent tuberculosis infection. Herein, we present a 76-year-old Brazilian male recently treated for COVID-19 pneumonia, presenting with new-onset cough and weakness diagnosed with latent MTB reactivation.

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“… 95 Other adverse events that are likely following tocilizumab therapy include LFTs elevation, absolute neutrophil count (ANC) and a reduction of platelets, infusion‐related adverse reactions, anaphylaxis, acute hypertriglyceridemia, ‏increased risk of latent TB reactivation, hepatitis B virus (HBV) reactivation, complications of the hepatitis C virus (HCV), hypotension, gastrointestinal (GI) perforation, and dyspnoea. 96 , 97 , 98 , 99 , 100 , 101 Recently, medication‐related osteonecrosis of the jaw (MRONJ) was identified as a rare complication of tocilizumab therapy. 102 Nonetheless, it should be reminded that in previous studies, tocilizumab was administered for a long‐term period [e.g., 48 weeks in Khanna et al.…”

Section: Safety Issues To Be Considered During Tocilizumab Therapymentioning

confidence: 99%

The role of cytokines and their antagonists in the treatment of COVID‐19 patients

Afshar

Barary

Babazadeh

et al. 2022

Reviews in Medical Virology

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The coronavirus disease 2019 (COVID‐19) has various presentations, of which immune dysregulation or the so‐called cytokine storm syndrome (COVID‐CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID‐19 infections, caused by the excessive release of pro‐inflammatory cytokines, such as interleukin‐1 (IL‐1), IL‐6, IL‐8, tumour necrosis factor, granulocyte‐macrophage colony‐stimulating factor, and interferon‐gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin‐6 receptor blocker approved to treat severe COVID‐19 infections.

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Risk of reactivation of hepatitis B virus (HBV) and tuberculosis (TB) and complications of hepatitis C virus (HCV) following Tocilizumab therapy: A systematic review to inform risk assessment in the COVID era

Cited by 6 publications

References 34 publications

Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Reactivation of Tuberculosis in the Setting of COVID-19 Infection

The role of cytokines and their antagonists in the treatment of COVID‐19 patients

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