dc.contributor
Institut Català de la Salut
dc.contributor
[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
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Montalban Gairín, Xavier
dc.contributor.author
Genovese, Mark C
dc.contributor.author
Parsons-Rich, Dana
dc.contributor.author
Le Bolay, Claire
dc.contributor.author
Kao, Amy H
dc.contributor.author
Guehring, Hans
dc.contributor.author
Wallace, Daniel
dc.contributor.author
Tomic, Davorka Lucia
dc.date.accessioned
2025-10-24T10:38:27Z
dc.date.available
2025-10-24T10:38:27Z
dc.date.issued
2023-02-22T12:53:05Z
dc.date.issued
2023-02-22T12:53:05Z
dc.identifier
Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Bolay C Le, et al. Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):1–9.
dc.identifier
https://hdl.handle.net/11351/9033
dc.identifier
10.1136/jnnp-2022-328799
dc.identifier
000890789300001
dc.identifier.uri
http://hdl.handle.net/11351/9033
dc.description.abstract
Immunology; Multiple sclerosis; Rheumatology
dc.description.abstract
Inmunología; Esclerosis múltiple; Reumatología
dc.description.abstract
Immunologia; Esclerosi múltiple; Reumatologia
dc.description.abstract
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.
dc.description.abstract
The trial was sponsored by Merck Healthcare KGaA (CrossRef Funder ID: 10.13039/100009945).
dc.format
application/pdf
dc.relation
Journal of Neurology, Neurosurgery & Psychiatry;94(1)
dc.relation
http://dx.doi.org/10.1136/jnnp-2022-328799
dc.rights
Attribution-NonCommercial 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Esclerosi múltiple - Tractament
dc.subject
Artritis reumatoide - Tractament
dc.subject
Lupus eritematós - Tractament
dc.subject
Proteïnes quinases - Inhibidors - Ús terapèutic
dc.subject
DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
dc.subject
DISEASES::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic
dc.subject
DISEASES::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid
dc.subject
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases
dc.subject
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
dc.subject
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple
dc.subject
ENFERMEDADES::enfermedades del sistema inmune::enfermedades autoinmunes::lupus eritematoso sistémico
dc.subject
ENFERMEDADES::enfermedades musculoesqueléticas::artropatías::artritis::artritis reumatoide
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
dc.title
Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
