Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studiesKristensen, Tillett, Nash
et alTher Adv Musculoskelet Dis (2024) 16, 1759720X241288071
Abstract: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR).To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab.Post hoc analysis of two phase III studies.BE OPTIMAL and BE COMPLETE assessed subcutaneous bimekizumab 160 mg every 4 weeks in bDMARD-naïve and TNFi-IR patients with active PsA. Disease control was assessed using American College of Rheumatology (ACR) response criteria, Minimal Disease Activity, Disease Activity Index for Psoriatic Arthritis, and the composite outcome of ACR50 and 100% improvement in Psoriasis Area and Severity Index. Associations between clinical disease control criteria and PRO measures of pain, fatigue, physical function, and HRQoL were assessed at week 16 and week 52/40 (BE OPTIMAL/BE COMPLETE).Achievement of increasingly stringent clinical disease control criteria was generally associated with sequentially greater improvements in all PRO measures, including pain. At week 52/40, 94.7% of bDMARD-naïve and 97.6% of TNFi-IR patients achieving ACR70 reported ⩾50% improvements in pain from baseline, and the greatest numerical improvements (-48.5 bDMARD-naïve; -54.7 TNFi-IR). This pattern was evident as early as week 16 and sustained when assessed at week 52/40 across the majority of clinical disease control criteria and PRO measures reported.The achievement of increasingly stringent thresholds of disease control was associated with corresponding greater improvements in PROs, for patients receiving bimekizumab treatment, irrespective of prior TNFi use.NCT03895203, NCT03896581, and NCT04009499.© The Author(s), 2024.
Bimekizumab for the treatment of hidradenitis suppurativaShams, Sayed
Immunotherapy (2024) 16 (16-17), 1005-1013
Abstract: Hidradenitis suppurativa (HS) is a painful, inflammatory dermatosis involving recurrent abscesses, nodules and tunnels in intertriginous regions. Biologics and other immunomodulators have significantly expanded the treatment options available for HS. Bimekizumab is a monoclonal antibody targeting both interleukin-17A and interleukin-17F, key mediators of inflammation, that is already approved for psoriasis, psoriatic arthritis and axial spondylarthritis. It is currently pending FDA review for HS treatment but has already received marketing authorization for this indication in Europe. This review aims to explore drug-specific characteristics of bimekizumab including its mechanism of action, pharmacokinetics and pharmacodynamics and the current state of the literature regarding its use in HS such as safety, efficacy and dosing, while highlighting its implications in clinical practice. Recent Phase II and III trial data demonstrating positive efficacy and safety profiles in the treatment of HS will also be detailed.
EIF4A3-induced hsa_circ_0078136 inhibits the tumorigenesis of retinoblastoma via IL-17 signaling pathwayChen, He, Cheng
et alInt Ophthalmol (2024) 44 (1), 352
Abstract: Retinoblastoma (RB) is one of the most common intraocular cancers, with the highest prevalence among infants and young children under the age five. Numerous findings across the literature illustrate the involvement and significance of circular RNAs (circRNAs) in human malignancies, including RB. The current investigation attempted to decipher the exact roles and underlying mechanisms of a novel circRNA, hsa_circ_0078136, in RB progression.The hsa_circ_0078136 expression was evaluated in RB tumors and cell lines via qRT-PCR. The significance of hsa_circ_0078136 in RB was examined by performing CCK8 assay, transwell assays, western blotting of apoptotic and IL-17 signaling ligand molecules, and a subcutaneous xenograft tumor model. In addition, the interaction of circRNA and eukaryotic translation initiation factor 4A3 (EIF4A3) was determined with bioinformatics, western blot, and RIP assay.The hsa_circ_0078136 expression was reduced in RB tumor samples and cells. Additionally, its overexpression restricted the oncogenic properties of RB cells in vitro. Moreover, hsa_circ_0078136 overexpression lowered the protein levels of cytokine ligand molecules of IL-17 signaling pathway in RB cell lines. In vivo, hsa_circ_0078136 overexpression in subcutaneous tumor xenografts reduced tumor growth. We also observed that EIF4A3 binds to the downstream flanking sequence of hsa_circ_0078136 in the SHRPH pre-mRNA transcript, and EIF4A3 overexpression reduced hsa_circ_0078136 expression, suggesting that EIF4A3 inhibited hsa_circ_0078136 formation.Our results demonstrate that hsa_circ_0078136 is regulated by EIF4A3 and functions as a tumor suppressor via the IL-17 signaling pathway in RB.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritisRamiro, Lukas, Bessette
et alRMD Open (2024) 10 (3)
Abstract: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE).This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data.Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52.This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52.NCT02696785.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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