Profile of sarilumab and its potential in the treatment of rheumatoid arthritis

Abstract

In recent years the use of biotechnological agents has drastically revolutionized the therapeutic approach and the progression of rheumatoid arthritis (RA). In particular, interleukin-6 (IL-6) has been demonstrated as a pivotal cytokine in the pathogenesis of the disease by contributing to both the innate and the adaptive immune system perturbation, and to the production of acute-phase proteins involved in the systemic expression of the disorder. The first marketed IL-6 blocker was tocilizumab, a humanized anti-IL-6 receptor (anti-IL-6R) monoclonal antibody. The successful use of tocilizumab in RA has encouraged the development of other biologic agents specifically targeting the IL-6 pathway, either directed against IL-6 cytokine (sirukumab, olokizumab, and clazakizumab) or IL-6 receptor (sarilumab). One Phase II and six Phase III randomized controlled trials demonstrated a broad efficacy of sarilumab across all RA patient subtypes, ranging from methotrexate (MTX) to tumor necrosis factor inhibitor insufficient responders. In particular, sarilumab as monotherapy demonstrated a clear head-to-head superiority over adalimumab in MTX-intolerant subjects. In addition, compared with tocilizumab, sarilumab showed a similar safety profile with significantly higher affinity and longer half-life, responsible for a reduction of the frequency of administration (every other week instead weekly). All these aspects may be important in defining the strategy for positioning sarilumab in the treatment algorithm of RA. Indeed, observational data coming from post-marketing real-life studies may provide crucial additional information for better understanding the role of sarilumab in the management of the disease. This review summarizes both the biological role of IL-6 in RA and the clinical data available on sarilumab as an alternative therapeutic option in RA patients.

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

“…Antibodies such as sarilumab, sirukumab, and siltuximab were developed to target IL6 for the treatment of RA or other diseases (58); however, these drugs have not yet been considered for use in the treatment of MG.…”

Confirmatory Population Pharmacokinetic Analysis for Sirukumab, a Human Monoclonal Antibody Targeting Interleukin‐6, in Patients With Moderately to Severely Active Rheumatoid Arthritis

“…The study duration was 120 weeks including a 104-week double-blind treatment phase and a 16-week follow-up phase. PK and immunogenicity data collected through week 52 were included in this analysis, including blood samplings for PK at weeks 0, 2,4,6,8,12,16,18,20,24,28,40, and 52 (plus a random sample between weeks 0 and 16), and immunogenicity samplings at weeks 0, 24, and 52. Approximately 70% of the patients randomized to the sirukumab treatment arms had PK samples collected, and thus, only data from these patients were included for the analysis.…”

“…The study duration was 68 weeks including a 52-week double-blind treatment phase and a 16-week follow-up phase. PK and immunogenicity data collected from sirukumab treatment arms through week 68 were included in this analysis, including blood samplings for PK at weeks 0, 2, 4, 6,8,12,16,18,20,24,36,44,52, and 68 (safety follow-up) (plus a random sample between weeks 0 and 16), and immunogenicity samplings at weeks 0, 24, 52, and 68 (safety follow-up).…”

“…2 One of the key components in the pathophysiology of RA is interleukin 6 (IL-6). 3 Targeting the IL-6 pathway has been proven effective for the treatment of RA as shown by anti-IL-6 receptor (IL-6R) mAbs such as tocilizumab 4,5 and sarilumab, 6 as well as a few kinase inhibitors affecting the signal transduction of IL- 6. 7 Sirukumab (CNTO136) is a human immunoglobulin G1κ (IgG1κ) mAb that binds to human IL-6 with high affinity and specificity.…”

Auswahl klinischer und diagnostischer Ergebnisse bei entzündlichen Gelenkerkrankungen

“…Einige Daten müssen noch ergänzend durch den Hersteller vorgelegt werden. Insgesamt zeigt sich auch hier eine deutliche Verbesserung in der RA-Symptomatik [44].…”