Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial
Abstract Background Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendro...
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| Format: | Article |
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BMC
2020-03-01
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| Series: | BMC Neurology |
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| Online Access: | http://link.springer.com/article/10.1186/s12883-020-01645-z |
| _version_ | 1818997983294783488 |
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| author | Christian Albert Janine Mikolajczak Anja Liekfeld Sophie K. Piper Michael Scheel Hanna G. Zimmermann Claus Nowak Jan Dörr Judith Bellmann-Strobl Claudia Chien Alexander U. Brandt Friedemann Paul Olaf Hoffmann |
| author_facet | Christian Albert Janine Mikolajczak Anja Liekfeld Sophie K. Piper Michael Scheel Hanna G. Zimmermann Claus Nowak Jan Dörr Judith Bellmann-Strobl Claudia Chien Alexander U. Brandt Friedemann Paul Olaf Hoffmann |
| author_sort | Christian Albert |
| collection | DOAJ |
| description | Abstract Background Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. Methods MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated syndrome or MS relapse, were randomized to 6 months of treatment with 0.5 mg oral fingolimod or subcutaneous IFN-β 1b 250 μg every other day. The change in multifocal visual evoked potential (mfVEP) latency of the qualifying eye was examined as the primary (month 6 vs. baseline) and secondary (months 3, 6 and 12 vs. baseline) outcome. In addition, full field visual evoked potentials, visual acuity, optical coherence tomography as well as clinical relapses and measures of disability, cerebral MRI, and self-reported visual quality of life were obtained for follow-up. The study was halted due to insufficient recruitment (n = 15), and available results are reported. Results Per protocol analysis of the primary endpoint revealed a significantly larger reduction of mfVEP latency at 6 months compared to baseline with fingolimod treatment (n = 5; median decrease, 15.7 ms) than with IFN-β 1b treatment (n = 4; median increase, 8.15 ms) (p < 0.001 for interaction). Statistical significance was maintained in the secondary endpoint analysis. Descriptive results are reported for other endpoints. Conclusion Preliminary results of the MOVING trial argue in support of a beneficial effect of fingolimod on optic nerve remyelination when compared to IFN-β treatment. Interpretation is limited by the small number of complete observations, an unexpected deterioration of the control group and a difference in baseline mfVEP latencies. The findings need to be confirmed in larger studies. Trial registration The trial was registered as EUDRA-CT 2011–004787-30 on October 26, 2012 and as NCT01647880 on July 24, 2012. |
| first_indexed | 2024-12-20T21:54:18Z |
| format | Article |
| id | doaj.art-2d7d38ec7298453fba53a4451db2975a |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-20T21:54:18Z |
| publishDate | 2020-03-01 |
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| series | BMC Neurology |
| spelling | doaj.art-2d7d38ec7298453fba53a4451db2975a2022-12-21T19:25:29ZengBMCBMC Neurology1471-23772020-03-0120111210.1186/s12883-020-01645-zFingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trialChristian Albert0Janine Mikolajczak1Anja Liekfeld2Sophie K. Piper3Michael Scheel4Hanna G. Zimmermann5Claus Nowak6Jan Dörr7Judith Bellmann-Strobl8Claudia Chien9Alexander U. Brandt10Friedemann Paul11Olaf Hoffmann12Department of Neurology, Alexianer St. Josefs-Krankenhaus PotsdamNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinDepartment of Ophthalmology, Klinikum Ernst von BergmannInstitute of Biometry and Clinical Epidemiology, Charité-Universitätmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinBerlin Institute of HealthNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinNeurocure Clinical Research Center, Charite-Universitätsmedizin BerlinDepartment of Neurology, Alexianer St. Josefs-Krankenhaus PotsdamAbstract Background Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. Methods MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated syndrome or MS relapse, were randomized to 6 months of treatment with 0.5 mg oral fingolimod or subcutaneous IFN-β 1b 250 μg every other day. The change in multifocal visual evoked potential (mfVEP) latency of the qualifying eye was examined as the primary (month 6 vs. baseline) and secondary (months 3, 6 and 12 vs. baseline) outcome. In addition, full field visual evoked potentials, visual acuity, optical coherence tomography as well as clinical relapses and measures of disability, cerebral MRI, and self-reported visual quality of life were obtained for follow-up. The study was halted due to insufficient recruitment (n = 15), and available results are reported. Results Per protocol analysis of the primary endpoint revealed a significantly larger reduction of mfVEP latency at 6 months compared to baseline with fingolimod treatment (n = 5; median decrease, 15.7 ms) than with IFN-β 1b treatment (n = 4; median increase, 8.15 ms) (p < 0.001 for interaction). Statistical significance was maintained in the secondary endpoint analysis. Descriptive results are reported for other endpoints. Conclusion Preliminary results of the MOVING trial argue in support of a beneficial effect of fingolimod on optic nerve remyelination when compared to IFN-β treatment. Interpretation is limited by the small number of complete observations, an unexpected deterioration of the control group and a difference in baseline mfVEP latencies. The findings need to be confirmed in larger studies. Trial registration The trial was registered as EUDRA-CT 2011–004787-30 on October 26, 2012 and as NCT01647880 on July 24, 2012.http://link.springer.com/article/10.1186/s12883-020-01645-zOptic neuritisFingolimodInterferon Beta-1bRemyelinationMultifocal VEP |
| spellingShingle | Christian Albert Janine Mikolajczak Anja Liekfeld Sophie K. Piper Michael Scheel Hanna G. Zimmermann Claus Nowak Jan Dörr Judith Bellmann-Strobl Claudia Chien Alexander U. Brandt Friedemann Paul Olaf Hoffmann Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial BMC Neurology Optic neuritis Fingolimod Interferon Beta-1b Remyelination Multifocal VEP |
| title | Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial |
| title_full | Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial |
| title_fullStr | Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial |
| title_full_unstemmed | Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial |
| title_short | Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) – preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial |
| title_sort | fingolimod after a first unilateral episode of acute optic neuritis moving preliminary results from a randomized rater blind active controlled phase 2 trial |
| topic | Optic neuritis Fingolimod Interferon Beta-1b Remyelination Multifocal VEP |
| url | http://link.springer.com/article/10.1186/s12883-020-01645-z |
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