https://doi.org/10.1016/j.intimp.2022.108536

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

Rheumatoid arthritis (RA) is a chronic immune-mediated rheumatic diseases (IMRDs) manifested with progressive destruction of joints, systemic inflammation of visceral organs and a wide range of co-morbidities associated with chronic inflammation. Among the cytokines involved in the pathogenesis of RA and certain other IMRDs, the role of interleukin (IL) 6 is of special interest. The introduction of mAbs tocilizumab (TCZ) and later sarilumab (SAR), both blocking the receptor of this cytokine, into clinical practice was an important achievement in the treatment of IIRDs at the beginning of the 21st century. As a novel approach in the treatment of RA, the humanized mAb against IL-6 olokizumab (OKZ) is in development by the Russian company R-PHARM under the license agreement with UCB Pharma. The review examines new data on efficacy and safety of OKZ in RA and the prospects of its use in rheumatology 

/pdf/the-prospects-of-interleukin-6-inhibition-in-rheumatoid-2i21ennm.pdf

The prospects of interleukin-6 inhibition in rheumatoid arthritis: Olokizumab (novel monoclonal antibodies to IL-6)

Coronavirus disease 2019 is a rather heterogeneous disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing pandemic is a global threat with increasing death tolls worldwide. SARS-CoV-2 belongs to lineage B β-CoV, a subgroup of Sarbecovirus. These enveloped, large, positive-sense single-stranded RNA viruses are easily spread among individuals, mainly via the respiratory system and droplets. Although the disease has been gradually controlled in many countries, once social restrictions are relaxed the virus may rebound, leading to a more severe and uncontrollable situation again, as occurred in Shanghai, China, in 2022. The current global health threat calls for the urgent development of effective therapeutic options for the treatment and prevention of SARS-CoV-2 infection. This systematic overview of possible SARS-CoV-2 therapeutic strategies from 2019 to 2022 indicates three potential targets: virus entry, virus replication, and the immune system. The information provided in this review will aid the development of more potent and specific antiviral compounds.

/pdf/a-review-of-potential-therapeutic-strategies-for-covid-19-12lpnby0.pdf

A Review of Potential Therapeutic Strategies for COVID-19

Coronavirus infection can have various degrees of severity and outcomes. In some cases, it causes excessive production of pro-inflammatory cytokines, a so-called cytokine storm, leading to acute respiratory distress syndrome. Unfortunately, the exact pathophysiology and treatment, especially for severe cases of COVID-19, are still uncertain. Results of preliminary studies showed that immunosuppressive therapy, such as interleukin (IL)-6, IL-1, and TNF-α antagonists commonly used in rheumatology, can be considered as treatment options for COVID-19, especially in severe cases. The review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm. It also covered effects of interleukin (IL)-6, IL-1, and TNF-α blockers on the course of coronavirus infection and outcome in patients treated for the main autoimmune disease and subsequently infected with COVID-19. 

/pdf/application-of-monoclonal-antibody-drugs-in-treatment-of-1dahq1pu.pdf

Application of Monoclonal Antibody Drugs in Treatment of COVID-19: a Review

Objective.
To evaluate safety of anti-interleukin drugs used as a pathogenetic therapy of COVID-19 as assessed by risks of infectious complications.

Materials and Methods.
A systematic review of publications related to safety assessment of anti-interleukin drugs recommended as pathogenetic therapy in COVID-19 patients in terms of incidence of serious adverse events and adverse events of “Infections and Invasions” class and a meta-analysis of the data were performed.

Results.
The meta-analysis included 16 randomized and 3 non-randomized studies. The hazard ratio of serious adverse events between the comparison groups was 0.93 95% CI 0.85; 1.01, the hazard ratio of adverse event of “Infections and Invasions” class was 0.9 95% CI 0.8; 1.02, showing no differences in the incidence of those events.

Conclusions.
This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of “Infections and Invasions” class for the use of antiinterleukin drugs in COVID-19 patients.

A systematic review and meta-analysis of the safety of anti-interleukin therapy in COVID-19

Most subjects with the COVID-19 experience mild to moderate symptoms, but approximately 10% of cases suffer from severe course of disease IL-6 inhibitors are actively used to neutralize and prevent the «cytokine storm» Olokizumab is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it Aim  To evaluate the efficacy and safety of Artlegia (olokizumab) for the treatment of subjects with a disease caused by the SARS-COV-2 virus in a real-world clinical setting Materials and methods  The analysis included data of 610 subjects aged 5508±1268 years who received olokizumab at a single dose of 160 mg/mL – 04 mL subcutaneously as a preemptive anti-inflammatory therapy The comparison group included 511 subjects aged 5523±1123 years who received standard therapy without IL-6 inhibitors Control Endpoints: 1 Positive clinical changes on Day 7 2 Changes in the CRP levels on Days 1, 2, and 7 3 Duration of oxygen therapy 4 Number of days in hospital 5 Number of adverse events 6 Disease outcome Results  If a «cytokine storm» occurs, immune regulatory events will trigger the development of either a protective immune response or an exacerbated inflammatory response The use of preemptive anti-inflammatory therapy has both a short-term and, most importantly, a long-term effect on the T and B parts of the immune process These aspects definitely require further research and observation Conclusion  The use of olokizumab to treat the new COVID-19 coronavirus disease has demonstrated a positive effect on clinical and laboratory parameters Primarily, it affects the severity of clinical parameters by improving the general condition already on the first day of observation, and decreasing body temperature to normal values The changes in the C-reactive protein levels show a significant effect of the IL-6 inhibitor on the systemic inflammatory response

https://ter-arkhiv.ru/0040-3660/article/viewFile/60284/43453

V V Khinovker

Papers

[Experience of olokizumab use in COVID-19 patients].