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• W3173747609 abstract "We thank Leah Rooney and colleagues for their interest in our phase 2 clinical trials of otilimab 1 Buckley CD Simón-Campos JA Zhdan V et al. Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study. Lancet Rheumatol. 2020; 2: e677-e688 Summary Full Text Full Text PDF Scopus (8) Google Scholar , 2 Genovese MC Berkowitz M Conaghan PG et al. MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatol. 2020; 2: e666-e676 Summary Full Text Full Text PDF Scopus (5) Google Scholar , 3 Schett G Bainbridge C Berkowitz M et al. Anti-granulocyte-macrophage colony-stimulating factor antibody otilimab in patients with hand osteoarthritis: a phase 2a randomised trial. Lancet Rheumatol. 2020; 2: e623-e632 Summary Full Text Full Text PDF Scopus (3) Google Scholar and for drawing attention to the theoretical risk of pulmonary alveolar proteinosis with the therapeutic targeting of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling. Targeting GM-CSF in rheumatological conditions: risk of PAPWe read with interest the three phase 2 trials of otilimab1–3 published in The Lancet Rheumatology. The identification of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a relevant target in rheumatological indications—in particular in rheumatoid arthritis—not only in the laboratory, but also now in phase 2 clinical trials, raises several clinical and scientific questions. Vivian P Bykerk has competently articulated many of these issues in her linked Comment,4 particularly the potential unknown effect of inhibiting this pleiotropic factor in the lung, as it is a pivotal protagonist in the inflammatory cascade. Full-Text PDF MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic studySerum concentrations of GM-CSF–otilimab complex indicated that target engagement was achieved with initial weekly dosing, but not sustained with every other week dosing. CCL17 might be a pharmacodynamic biomarker for otilimab activity in future studies. Otilimab was well tolerated and, despite suboptimal exposure, showed some evidence for improved synovitis over 12 weeks in patients with active rheumatoid arthritis. Full-Text PDF" @default.
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• W3173747609 date "2021-07-01" @default.
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• W3173747609 title "Targeting GM-CSF in rheumatological conditions: risk of PAP – Authors' reply" @default.
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• W3173747609 doi "https://doi.org/10.1016/s2665-9913(21)00146-6" @default.
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