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Rheumatoid Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Brent A. Luedders, Ted R. Mikuls, James R. O’Dell, Bryant R. England
Further insights into the pathogenesis of RA will lead to novel discoveries, including perhaps more precise targets for RA therapies. Targeting the pathways most directly involved in causing RA can produce better efficacy, lower toxicities, and promote the pursuit of cures over treatments. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine involved in the production and maturation of bone marrow myeloid cells and regulates mature myeloid cell functions, both implicated in the pathogenesis of RA.50 Several biologic agents targeting the GM-CSF pathway are currently under investigation for RA. Both mavrilimumab and otilimab have shown efficacy in phase 1 and 2 clinical trials.137–139
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Since GM-CSF is widely recognized as a key mediator in inflammation and is secreted by a variety of cells, a single intravenous dose of mavrilimumab improved oxygenation and reduced hospitalization in COVID-19 patients. Thirteen non-mechanically ventilated patients with median age of 57 years (IQR 52–58) were given mavrilimumab. Compared to the control group of 26 patients with similar characteristics who did not receive mavrilimumab, the thirteen treated patients showed earlier improvement. The study concluded the result of eight days mean time to improvement in patients treated with mavrilimumab. The treatment was well received, as mavrilimumab therapy presented clinical benefits in patients with serious COVID-19 pneumonia and systemic hyperinflammation [32].
Mavrilimumab: a unique insight and update on the current status in the treatment of rheumatoid arthritis
Published in Expert Opinion on Investigational Drugs, 2019
Chiara Crotti, Martina Biggioggero, Andrea Becciolini, Elena Agape, Ennio Giulio Favalli
In the EARTH study [51], five serious AEs were observed: four (one spontaneous abortion, one intervertebral disc disorder, one fracture of the patella, and one fracture of the humerus) in the mavrilimumab group, and one (worsening of RA) in the placebo group (none considered treatment related). Low-titer and transient anti-mavrilimumab antibodies were reported in 23 patients (20 of 158 in the active treatment and 3 of 75 in the placebo groups) but they seemed to have no impact on the pharmacokinetics. High-titer antidrug antibodies were observed in one placebo (1.3%) and 10 mavrilimumab (6.3%; 3 at 10 mg, 4 at 30 mg, 1 at 50 mg, and 2 at 100mg) patients, with no correlation with tolerability and administration reaction [51]. Similarly, in the Japanese EARTH study [52], 22 treatment-emergent AEs were reported (16 [47.1%] in the mavrilimumab group versus 6 [35.3%] in the placebo group), with only one serious AE (pneumonia) leading to mavrilimumab withdrawal [52].
Giant cell arteritis: what is new in the preclinical and early clinical development pipeline?
Published in Expert Opinion on Investigational Drugs, 2022
Patricia Harkins, Richard Conway
Mavrilimumab is a GM-CSF inhibitor, previously studied in rheumatoid arthritis. The preliminary results of the ongoing phase 2 RCT in GCA have demonstrated results broadly in line with the effect size seen with tocilizumab and an overall favorable safety profile [80]. Abatacept has demonstrated efficacy in GCA in a previous RCT, this had a slightly unusual withdrawal design complicating the interpretation of the study results [63]. A recently commenced phase 3 RCT should provide some clarity in this area. Ustekinumab has to date been studies in two pilot studies with contrasting results [54–56]. Again, an ongoing RCT will ascertain if the theoretically attractive pathophysiologic rationale for the use of ustekinumab in GCA translates to clinical efficacy.