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
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Wallace, Daniel (University of California)
Genovese, Mark C. (Stanford University)
Tomic, Davorka Lucia (Ares Trading SA)
Parsons-Rich, Dana (EMD Serono Research & Development Institute)
Le Bolay, Claire (Merck Healthcare KGaA)
Kao, Amy H. (EMD Serono Research & Development Institute)
Guehring, Hans (Merck Healthcare KGaA)
Universitat Autònoma de Barcelona

Fecha:	2022
Descripción:	9 pàg.
Resumen:	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. Trial registration numbers NCT02975349, NCT03233230, NCT02975336.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Immunology ; Multiple sclerosis ; Rheumatology ; SLE
Publicado en:	Journal of Neurology, Neurosurgery, and Psychiatry, Vol. 94 Núm. 1 (2022) , p. 1-9, ISSN 1468-330X

DOI: 10.1136/jnnp-2022-328799
PMID: 36418156

9 p, 608.1 KB

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