Sistema de Salut de Catalunya
Institut Català de la Salut
[Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Wallace D] Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [Genovese MC] Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA. [Tomic D] Global Clinical Development, Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA. [Parsons-Rich D] Global Clinical Development, EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA, an affiliate of Merck KGaA (affiliation at the time the research was conducted). ECD-Early Clinical Development, Pfizer, Cambridge, Massachusetts, USA. [Le Bolay C] Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany. [Kao AH] Translational Innovation Platform in Immunology & Neuroscience, EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA, an affiliate of Merck KGaA. [Guehring H] Global Patient Safety, Merck Healthcare KGaA, Darmstadt, Germany
Vall d'Hebron Barcelona Hospital Campus
2023-02-22T12:53:05Z
2023-02-22T12:53:05Z
2023-01
Immunology; Multiple sclerosis; Rheumatology
Inmunología; Esclerosis múltiple; Reumatología
Immunologia; Esclerosi múltiple; Reumatologia
Objective Analyse the integrated safety profile of evobrutinib, a Bruton’s tyrosine kinase inhibitor (BTKi), using pooled data from multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) trials. Methods Phase II, randomised, double-blind, placebo-controlled trial data were analysed (N=1083; MS: n=213, 48 weeks (W); RA: n=390, 12W; SLE: n=480, 52W). The analysis included all patients who received ≥1 dose of evobrutinib (25 mg or 75 mg once daily, or 50 mg or 75 mgtwice daily) or placebo. Descriptive statistics and exposure-adjusted incidence rates (EAIR) were used to report treatment-emergent adverse events (TEAEs). Results Data from 1083 patients were pooled: evobrutinib, n=861; placebo, n=271 (sum >1083 due to MS trial design: n=49 received both placebo (W0–24) and evobrutinib 25 mg (W25–48)); median follow-up time (pt-years): evobrutinib, 0.501; placebo, 0.463. Across indications, the proportion of patients with TEAEs and the EAIR were similar for evobrutinib and placebo (66.2% (247.6 events/100 pt-years) vs 62.4% (261.4 events/100 pt-years)). By indication, the EAIR (events/100 pt-years) of TEAEs for evobrutinib versus placebo were: MS: 119.7 vs 148.3; RA: 331.8 vs 306.8; SLE: 343.0 vs 302.1. Two fatal events occurred (in SLE). The serious infections EAIR was 2.7 and 2.1 events/100 pt-years for evobrutinib and placebo. For previously reported BTKi-class effects, the EAIR of transient elevated alanine aminotransferase/aspartate aminotransferase TEAEs (events/100 pt-years) with evobrutinib versus placebo was 4.8 vs 2.8/3.5 vs 0.7, respectively. IgG levels were similar in evobrutinib/placebo-treated patients. Conclusions This is the first BTKi-integrated safety analysis that includes patients with MS. Overall, evobrutinib treatment (all doses) was generally well tolerated across indications.
The trial was sponsored by Merck Healthcare KGaA (CrossRef Funder ID: 10.13039/100009945).
Artículo
Versión publicada
Inglés
Esclerosi múltiple - Tractament; Artritis reumatoide - Tractament; Lupus eritematós - Tractament; Proteïnes quinases - Inhibidors - Ús terapèutic; DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis; DISEASES::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic; DISEASES::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid; CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases; Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple; ENFERMEDADES::enfermedades del sistema inmune::enfermedades autoinmunes::lupus eritematoso sistémico; ENFERMEDADES::enfermedades musculoesqueléticas::artropatías::artritis::artritis reumatoide; COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas; Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
BMJ
Journal of Neurology, Neurosurgery & Psychiatry;94(1)
http://dx.doi.org/10.1136/jnnp-2022-328799
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
Articles científics - CEMCAT [136]
Articles científics - HVH [3396]
