Ozanimod in relapsing multiple sclerosis
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 ra...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:276012 |
| Acesso em linha: | https://ddd.uab.cat/record/276012 https://dx.doi.org/urn:doi:10.1016/j.msard.2021.102844 |
| Access Level: | acceso abierto |
| Palavra-chave: | Multiple sclerosis Ozanimod Safety Adverse events Clinical trials |
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Ozanimod in relapsing multiple sclerosisPooled safety results from the clinical development programSelmaj, Krzysztof W.|||0000-0003-1213-7218Cohen, Jeffrey A.|||0000-0001-9245-9772Comi, Giancarlo|||0000-0002-6989-1054Bar-Or, Amit|||0000-0001-7179-0335Arnold, Douglas Lorne|||0000-0003-4266-0106Steinman, Lawrence|||0000-0002-2437-2250Hartung, Hans-Peter|||0000-0002-0614-6989Montalban, Xavier|||0000-0002-0098-9918Kubala Havrdova, Eva|||0000-0002-9543-4359Cree, Bruce A. C.|||0000-0001-7689-2533Minton, NeilSheffield, James K.Ding, NingKappos, Ludwig|||0000-0003-4175-5509Multiple sclerosisOzanimodSafetyAdverse eventsClinical trialsBackground: 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.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/276012https://dx.doi.org/urn:doi:10.1016/j.msard.2021.102844reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2760122026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Ozanimod in relapsing multiple sclerosis Pooled safety results from the clinical development program |
| title |
Ozanimod in relapsing multiple sclerosis |
| spellingShingle |
Ozanimod in relapsing multiple sclerosis Selmaj, Krzysztof W.|||0000-0003-1213-7218 Multiple sclerosis Ozanimod Safety Adverse events Clinical trials |
| title_short |
Ozanimod in relapsing multiple sclerosis |
| title_full |
Ozanimod in relapsing multiple sclerosis |
| title_fullStr |
Ozanimod in relapsing multiple sclerosis |
| title_full_unstemmed |
Ozanimod in relapsing multiple sclerosis |
| title_sort |
Ozanimod in relapsing multiple sclerosis |
| dc.creator.none.fl_str_mv |
Selmaj, Krzysztof W.|||0000-0003-1213-7218 Cohen, Jeffrey A.|||0000-0001-9245-9772 Comi, Giancarlo|||0000-0002-6989-1054 Bar-Or, Amit|||0000-0001-7179-0335 Arnold, Douglas Lorne|||0000-0003-4266-0106 Steinman, Lawrence|||0000-0002-2437-2250 Hartung, Hans-Peter|||0000-0002-0614-6989 Montalban, Xavier|||0000-0002-0098-9918 Kubala Havrdova, Eva|||0000-0002-9543-4359 Cree, Bruce A. C.|||0000-0001-7689-2533 Minton, Neil Sheffield, James K. Ding, Ning Kappos, Ludwig|||0000-0003-4175-5509 |
| author |
Selmaj, Krzysztof W.|||0000-0003-1213-7218 |
| author_facet |
Selmaj, Krzysztof W.|||0000-0003-1213-7218 Cohen, Jeffrey A.|||0000-0001-9245-9772 Comi, Giancarlo|||0000-0002-6989-1054 Bar-Or, Amit|||0000-0001-7179-0335 Arnold, Douglas Lorne|||0000-0003-4266-0106 Steinman, Lawrence|||0000-0002-2437-2250 Hartung, Hans-Peter|||0000-0002-0614-6989 Montalban, Xavier|||0000-0002-0098-9918 Kubala Havrdova, Eva|||0000-0002-9543-4359 Cree, Bruce A. C.|||0000-0001-7689-2533 Minton, Neil Sheffield, James K. Ding, Ning Kappos, Ludwig|||0000-0003-4175-5509 |
| author_role |
author |
| author2 |
Cohen, Jeffrey A.|||0000-0001-9245-9772 Comi, Giancarlo|||0000-0002-6989-1054 Bar-Or, Amit|||0000-0001-7179-0335 Arnold, Douglas Lorne|||0000-0003-4266-0106 Steinman, Lawrence|||0000-0002-2437-2250 Hartung, Hans-Peter|||0000-0002-0614-6989 Montalban, Xavier|||0000-0002-0098-9918 Kubala Havrdova, Eva|||0000-0002-9543-4359 Cree, Bruce A. C.|||0000-0001-7689-2533 Minton, Neil Sheffield, James K. Ding, Ning Kappos, Ludwig|||0000-0003-4175-5509 |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Multiple sclerosis Ozanimod Safety Adverse events Clinical trials |
| topic |
Multiple sclerosis Ozanimod Safety Adverse events Clinical trials |
| description |
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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/276012 https://dx.doi.org/urn:doi:10.1016/j.msard.2021.102844 |
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https://ddd.uab.cat/record/276012 https://dx.doi.org/urn:doi:10.1016/j.msard.2021.102844 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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