Ozanimod in relapsing multiple sclerosis : Pooled safety results from the clinical development program
Selmaj, Krzysztof W. (University of Warmia and Mazury)
Cohen, Jeffrey A. (Neurological Institute)
Comi, Giancarlo (Vita-Salute San Raffaele University)
Bar-Or, Amit (University of Pennsylvania)
Arnold, Douglas Lorne (McGill University)
Steinman, Lawrence (Stanford University Medical Center)
Hartung, Hans-Peter (Medical University Vienna)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Kubala Havrdova, Eva (Charles University)
Cree, Bruce A. C (UCSF University of California San Francisco)
Minton, Neil (Bristol Myers Squibb)
Sheffield, James K. (Bristol Myers Squibb)
Ding, Ning (Bristol Myers Squibb)
Kappos, Ludwig (University of Basel)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data. Methods: We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data. Results: At the data cutoff, 2631 RMS participants had exposure to ozanimod 0. 92 mg (mean 32. 0 months) and 2787 had exposure to either ozanimod 0. 46 or 0. 92 mg (mean 37. 1 months). The IRs per 1000 person-years (PY) for any TEAE (772. 2) and serious TEAEs (33. 2) in the overall population were similar to those in the phase 3 population (896. 1 and 31. 2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE. Conclusions: Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.
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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Multiple sclerosis ; Ozanimod ; Safety ; Adverse events ; Clinical trials
Publicado en:	Multiple Sclerosis and Related Disorders, Vol. 51 (june 2021) , p. 102844, ISSN 2211-0356

DOI: 10.1016/j.msard.2021.102844
PMID: 33892317

10 p, 683.9 KB

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