Tocilizumab in transplantation

Mosharmovahed, Banafsheh; Fatahi, Yousef; Mohebbi, Bahareh; Ghorbanian, Sohrab Ali; Assadiasl, Sara

doi:10.1007/s00228-020-02864-6

Cited by 11 publications

(11 citation statements)

References 67 publications

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“…IL-6 is an important pro-inflammatory cytokine that is involved in the acute phase response and differentiation and function of B and T cells ( Mosharmovahed et al., 2020 ). Of the three commercially available IL-6 inhibitors (tocilizumab, sarilumab and siltuximab), tocilizumab is the most well-known ( Khiali et al., 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…There is growing interest in IL-6 inhibitors, like tocilizumab. Patients with severe COVID-19 have high levels of IL-6 ( Mosharmovahed et al., 2020 ) and in three cohort studies, tocilizumab use was associated with lower mortality and ICU admission rate ( Capra et al., 2020 ; Klopfenstein et al., 2020 ; Moreno-García et al., 2020 ). However, other cohort studies report contradictory results ( Campochiaro et al., 2020 ; Colaneri et al., 2020 ; Della-Torre et al., 2020 ; Giacobbe et al., 2020 ; Quartuccio et al., 2020 ; Rojas-Marte et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Immunosuppressive Drugs and COVID-19: A Review

et al. 2020

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Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the “cytokine storm”) can cause ARDS, multiorgan failure and mortality. Aim To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) Methods The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group. Results and Conclusion Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro . Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo . There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunosuppressive Drugs and COVID-19: A Review

et al. 2020

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“…IL-6 consists of 184 amino acids in addition to a 28 amino acid signal peptide [ 16 ]. It utilizes unique signaling mechanisms including classical, trans-signaling, and trans-presentation pathways [ 8 , 17 , 18 ]. The IL-6 receptor (IL-6R) forms a complex of molecules consisting of gp80 and gp130 components; the gp80 subunit directly binds to IL-6 and is generally identified as IL-6R and relies on the gp130 component for signal transduction.…”

Section: Diverse Il-6 Signaling Pathwaysmentioning

confidence: 99%

IL-6 Directed Therapy in Transplantation

Miller

Madsen

2021

Curr Transpl Rep

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Purpose of Review IL-6 is a pleiotropic, pro-inflammatory cytokine that plays an integral role in the development of acute and chronic rejection after solid organ transplantation. This article reviews the experimental evidence and current clinical application of IL-6/IL-6 receptor (IL-6R) signaling inhibition for the prevention and treatment of allograft injury. Recent Findings There exists a robust body of evidence linking IL-6 to allograft injury mediated by acute inflammation, adaptive cellular/humoral responses, innate immunity, and fibrosis. IL-6 promotes the acute phase reaction, induces B cell maturation/antibody formation, directs cytotoxic T-cell differentiation, and inhibits regulatory T-cell development. Importantly, blockade of the IL-6/IL-6R signaling pathway has been shown to mitigate its harmful effects in experimental studies, particularly in models of kidney and heart transplant rejection. Currently, available agents for IL-6 signaling inhibition include monoclonal antibodies against IL-6 or IL-6R and janus kinase inhibitors. Recent clinical trials have investigated the use of tocilizumab, an anti-IL-6R mAb, for desensitization and treatment of antibody-mediated rejection (AMR) in kidney transplant recipients, with promising initial results. Further studies are underway investigating the use of alternative agents including clazakizumab, an anti-IL-6 mAb, and application of IL-6 signaling blockade to clinical cardiac transplantation. Summary IL-6/IL-6R signaling inhibition provides a novel therapeutic option for the prevention and treatment of allograft injury. To date, evidence from clinical trials supports the use of IL-6 blockade for desensitization and treatment of AMR in kidney transplant recipients. Ongoing and future clinical trials will further elucidate the role of IL-6 signaling inhibition in other types of solid organ transplantation.

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“…Notably, serious adverse events and new infections were less frequent in the combination group, revealing the superiority of baricitinib plus remdesivir therapy compared with remdesivir plus placebo 58 . Tocilizumab is an anti‐IL‐6 receptor antibody applied for inhibiting uncontrolled inflammatory responses such as cytokine storm following hematopoietic stem cell transplantation 59 . A retrospective study, treating the COVID‐19 patients admitted for interstitial pneumonia with baricitinib and/or tocilizumab (in addition to standard antiviral therapy) demonstrated the lowest death rate in patients receiving baricitinib.…”

Section: Coronavirus Disease‐19mentioning

confidence: 99%

Baricitinib: From Rheumatoid Arthritis to COVID‐19

Assadiasl

Fatahi

Mosharmovahed

et al. 2021

The Journal of Clinical Pharma

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Baricitinib is a JAK1/2 inhibitor first approved for treating moderate to severe rheumatoid arthritis but later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including rheumatoid arthritis, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated auto-inflammatory diseases, graft versus host disease, diabetic kidney disease, and recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib on one hand and the probable adverse effects, on the other hand, urge for further investigations before establishing it as a part of standard therapeutic protocols.Herein, we have provided a review of the studies which have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.

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Tocilizumab in transplantation

Cited by 11 publications

References 67 publications

Immunosuppressive Drugs and COVID-19: A Review

Immunosuppressive Drugs and COVID-19: A Review

IL-6 Directed Therapy in Transplantation

Baricitinib: From Rheumatoid Arthritis to COVID‐19

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