Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis: Long-term follow-up of a Phase II randomised clinical trial with a cerebrospinal fluid sub-study.
Mult Scler
; 30(4-5): 558-570, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38436271
ABSTRACT
BACKGROUND:
Evobrutinib - an oral, central nervous system (CNS)-penetrant, and highly selective Bruton's tyrosine kinase inhibitor - has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS.OBJECTIVE:
Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal fluid (CSF) sub-study.METHODS:
In the 48-week double-blind period (DBP), patients received evobrutinib 25 mg once-daily, 75 mg once-daily, 75 mg twice-daily or placebo (switched to evobrutinib 25 mg once-daily after week 24). Patients could then enter the OLE, receiving evobrutinib 75 mg once-daily (mean (± standard deviation (SD)) duration = 50.6 weeks (±6.0)) before switching to 75 mg twice-daily.RESULTS:
Of 164 evobrutinib-treated patients who entered the OLE, 128 (78.0%) completed ⩾192 weeks of treatment. Patients receiving DBP evobrutinib 75 mg twice-daily annualised relapse rate at week 48 (0.11 (95% confidence interval (CI) = 0.04-0.25)) was maintained with the OLE twice-daily dose up to week 192 (0.11 (0.05-0.22)); Expanded Disability Status Scale score remained stable; serum neurofilament light chain fell to levels like a non-MS population (Z-scores); T1 gadolinium-enhancing lesion numbers remained low. No new safety signals were identified. In the OLE, evobrutinib was detected in the CSF of all sub-study patients.CONCLUSION:
Long-term evobrutinib treatment was well tolerated and associated with a sustained low level of disease activity. Evobrutinib was present in CSF at concentrations similar to plasma.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Pirimidinas
/
Esclerose Múltipla
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article