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Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Anakinra is an antagonist for the interleukin IL-1 receptor. This recombinant antibody is used to treat autoinflammatory disorders by blocking the action of IL-1α and IL-1β (proinflammatory cytokines). Anakinra has the advantage of a shorter half-life compared to other cytokine blockers and is therefore suitable for the treatment of critically ill patients [25]. Treatment with high-dose Anakinra was linked to lower serum C-reactive protein levels and improved respiratory function over time (72%) in a retrospective longitudinal analysis of COVID-19 patients with ARDS and hyperinflammation [26]. In addition, the high-dose anakinra group had a survival rate of 90%, while the standard treatment group showed a survival rate of 56% [26] (Table 8.2).
Connective tissue disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
There is currently insufficient evidence on anakinra (an IL-1 receptor antagonist), abatacept (an inhibitor of T-cell co-stimulation), tocilizumab, golimumab or belimumab in pregnancy to inform clear recommendations about their use.
Treatment of Rheumatoid Arthritis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Stuart Weisman, Arthur Kavanaugh
In rheumatoid arthritis, IL-lβ is present in large quantities in the synovial fluid and synovial tissue.47 Interleukin-1 β can stimulate metalloproteinase expression, adhesion molecule expression, secretion of other cytokines, and prostaglandin production. Interleukin 1 receptor antagonist is a naturally occurring competitive inhibitor for IL-la and IL-lβ. IL-1 Ra binds to the IL-1R1 (interleukin-1 receptor) without transducing a signal, thus blocking the ability of interleukin la or 1 β to bind to the receptor. In November 2001, anakinra was approved for the treatment of rheumatoid arthritis. Anakinra is a recombinant form of the naturally occurring interleukin-1 receptor antagonist (ILl-Ra) produced using E. coli.
Advancements in the pharmacological management of sepsis in the elderly
Published in Expert Opinion on Pharmacotherapy, 2023
Christos Psarrakis, Evangelos J. Giamarellos-Bourboulis
The favorable perspective of precision immunotherapy was documented during the pandemic by the SARS-CoV-2 virus (COVID-19 disease). In the pivotal SAVE-MORE RCT, patients with COVID-19 pneumonia at risk for severe respiratory failure and death were 1:2 randomized to treatment with SoC and placebo or SoC and anakinra. Risk was defined as blood levels of the biomarker suPAR (soluble urokinase plasminogen activator receptor) 6 ng/ml or more. These levels are indicative of early activation of the IL-1 pathway [92]. Anakinra was administered as 100 mg subcutaneous injection once daily for 10 days. Results showed 0.36 odds ratio for worse outcome with anakinra treatment compared to placebo as this is expressed by the WHO clinical progression scale [93]. This is the first-in-class approach of a precision immunotherapy strategy for severe infections approved by both the European Medicines Agency and by the Food and Drug Administration of the US [94,95]. A recent sub-group analysis showed that the clinical benefit was similar for both elderly and non-elderly patients and both for patients with comorbidities and for patients without comorbidities [96].
Amyloid nomenclature 2022: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee
Published in Amyloid, 2022
Joel N. Buxbaum, Angela Dispenzieri, David S. Eisenberg, Marcus Fändrich, Giampaolo Merlini, Maria J. M. Saraiva, Yoshiki Sekijima, Per Westermark
Interleukin-1 is a prominent proinflammatory cytokine which is over-expressed in a number of inflammatory diseases, e.g. in auto-inflammatory disorders and in rheumatoid arthritis. Interleukin-1 receptor antagonist protein is expressed as a 177 aa protein including a 25 aa signal peptide. Anakinra is a recombinant analog, which binds to the IL-1 receptor and thereby exerts anti-inflammatory properties and is used therapeutically in rheumatoid arthritis and a variety of inflammatory disorders. The drug is given subcutaneously with one daily dose 100 mg which may vary according to the patients’ clinical status. In a recent report two patients were described with pronounced localised subcutaneous amyloid deposits at the site of injections [21]. Mass spectrometric analyses showed these to be of Interleukin-1 receptor antagonist protein nature. The name of the amyloid fibril protein is AIL1RAP.
Emerging therapies for COVID-19 pneumonia
Published in Expert Opinion on Investigational Drugs, 2020
Denise Battaglini, Chiara Robba, Lorenzo Ball, Fernanda Ferreira Cruz, Pedro Leme Silva, Paolo Pelosi, Patricia Rieken Macedo Rocco
The use of corticosteroids to modulate the inflammatory response in COVID-19 remains controversial. Based on an expert consensus [12–14], their use should be carefully weighed, according to clinical evidence: in patients already taking corticosteroids for chronic diseases, increased use should be evaluated with caution, with doses not exceed 0.5–1 mg/kg/day (methylprednisolone or equivalent) and for no longer than 7 days. The safety and efficacy of methylprednisolone in COVID-19 patients have been investigated in the clinical setting (Table 1). Interleukin (IL)-6 plays a crucial role in the inflammatory response, showing both anti-and pro-inflammatory effects on cells that express the IL-6 receptor (IL-6R), such as macrophages, neutrophils, and T-cells. Tocilizumab, a recombinant humanized monoclonal antibody, is designed to bind IL-6R. In 2017, it was approved for the treatment of cytokine release syndrome, which has prompted its possible use for COVID-19 in patients with higher levels of IL-6; efficacy remains unclear and requires confirmation [3]. Anakinra, an IL-1 receptor inhibitor, may likewise induce a short-term reversible suppression of inflammation. However, both of these drugs might increase the risk of superinfections, making their clinical use for COVID-19 questionable [3]. Bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, has been studied in COVID-19 patients to reduce lung edema [15].