Lessons learned from the preclinical discovery and development of sarilumab for the treatment of rheumatoid arthritis
| Autor: | Gabriella Maioli, Roberto Caporali, Ennio Giulio Favalli |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
rheumatoid arthritis
randomized clinical trials humanized antirheumatic agents rheumatoid interleukin-6 Antibodies Monoclonal interleukin 6 sarilumab monoclonal Antibodies Monoclonal Humanized IL-6 inhibitors Arthritis Rheumatoid Settore MED/16 - Reumatologia bDMARDs antibodies monoclonal antibodies monoclonal humanized humans treatment outcome arthritis rheumatoid arthritis Drug Discovery antibodies |
| Zdroj: | Expert Opinion on Drug Discovery. 17:799-813 |
| ISSN: | 1746-045X 1746-0441 |
| DOI: | 10.1080/17460441.2022.2093852 |
| Popis: | Rheumatoid arthritis (RA) pathogenesis is driven by a complex network of proinflammatory cytokines, among which interleukin-6 (IL-6) plays a key role in inducing and perpetuating chronic inflammation. Targeting the IL-6 pathway has shown to be an invaluable treatment strategy, as demonstrated by the results accrued in the last decade with the first IL-6 inhibitor, tocilizumab. More recently, a second monoclonal antibody blocking IL-6, sarilumab, has enriched our armamentarium by proving outstanding efficacy in RA treatment.After exploring the IL-6 pathway under physiological conditions and in the RA pathogenesis, in this review we discuss the pharmacologic properties of sarilumab and the clinical trials that constitute the sarilumab development program and have enabled its licensed application.Results from clinical trials confirmed the efficacy and safety of sarilumab for the treatment of RA, similar to its precursor tocilizumab. Blocking IL-6 pathway results in comprehensive control of the disease, from both physician's and patient's perspective, and of RA comorbidities and extra-articular manifestations, which are largely IL-6 driven. Finally, the proven efficacy of sarilumab as monotherapy arises the drug as a required therapeutic alternative considering the large proportion of patients intolerant or inadequate to receive conventional synthetic disease-modifying drugs (csDMARDs). |
| Databáze: | OpenAIRE |
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